Homeostatic mechanisms work to maintain steady internal conditions in the body. They utilize negative feedback systems to counteract changes and return to the normal setpoint. Homeostasis involves reflexes, local responses, and chemical messengers like hormones and neurotransmitters. Receptors on cells detect messengers and trigger signal transduction pathways, ultimately causing cellular responses. This maintains balance and stability within the body.
Human Anatomy and Physiology : Introduction
PCI Syllabus, B. Pharmacy, BP101T
Session VI
Basic life processes, Metabolism, growth, responsiveness, differentiation, movement, reproduction.
Homeostasis. Definition, regulation, feedback system. Disorders, diseases and death. Signs and Symptoms.
Human Anatomy and Physiology : Introduction
PCI Syllabus, B. Pharmacy, BP101T
Session VI
Basic life processes, Metabolism, growth, responsiveness, differentiation, movement, reproduction.
Homeostasis. Definition, regulation, feedback system. Disorders, diseases and death. Signs and Symptoms.
The cell was first discovered and named by Robert Hooke in 1665.
He remarked that it looked strangely similar to cellula or small rooms which monks inhabited, thus deriving the name. However what Hooke actually saw was the dead cell walls of plant cells (cork) as it appeared under the microscope.
surface Anatomy: The study of anatomical landmarks that can be identified by observing the surface of the body. Sometimes called superficial anatomy.
microscopic anatomy: The study of minute anatomical structures on a microscopic scale, including cells (cytology) and tissues (histology).
Gross (or macroscopic) anatomy: The study of anatomical features visible to the naked eye, such as internal organs and external features.
embryology: The science of the development of an embryo from the fertilization of the ovum to the fetal stage.
dissection: The process of disassembling an organism to determine its internal structure and understand the functions and relationships of its components.
surface Anatomy: The study of anatomical landmarks that can be identified by observing the surface of the body. Sometimes called superficial anatomy.
microscopic anatomy: The study of minute anatomical structures on a microscopic scale, including cells (cytology) and tissues (histology).
Gross (or macroscopic) anatomy: The study of anatomical features visible to the naked eye, such as internal organs and external features.
embryology: The science of the development of an embryo from the fertilization of the ovum to the fetal stage.
dissection: The process of disassembling an organism to determine its internal structure and understand the functions and relationships of its components.
The cell was first discovered and named by Robert Hooke in 1665.
He remarked that it looked strangely similar to cellula or small rooms which monks inhabited, thus deriving the name. However what Hooke actually saw was the dead cell walls of plant cells (cork) as it appeared under the microscope.
surface Anatomy: The study of anatomical landmarks that can be identified by observing the surface of the body. Sometimes called superficial anatomy.
microscopic anatomy: The study of minute anatomical structures on a microscopic scale, including cells (cytology) and tissues (histology).
Gross (or macroscopic) anatomy: The study of anatomical features visible to the naked eye, such as internal organs and external features.
embryology: The science of the development of an embryo from the fertilization of the ovum to the fetal stage.
dissection: The process of disassembling an organism to determine its internal structure and understand the functions and relationships of its components.
surface Anatomy: The study of anatomical landmarks that can be identified by observing the surface of the body. Sometimes called superficial anatomy.
microscopic anatomy: The study of minute anatomical structures on a microscopic scale, including cells (cytology) and tissues (histology).
Gross (or macroscopic) anatomy: The study of anatomical features visible to the naked eye, such as internal organs and external features.
embryology: The science of the development of an embryo from the fertilization of the ovum to the fetal stage.
dissection: The process of disassembling an organism to determine its internal structure and understand the functions and relationships of its components.
the structure of and formation blood cells, erythrocyte,leucocyte,neutrophil,basophil,eosinophil,lymphocyte T,lymphocyte B, hematopoiesis, erythropoiesis,leucopoiesis,granulocytopoiesis,agranulocytopoiesis,lymphopoiesis
THIS WILL HELP YOU ANALYSE HOMEOSTASIS COMPIELED IN A VERY REFINED FORM.
The tendency to maintain a stable, relatively constant internal environment is called homeostasis. The body maintains homeostasis for many factors in addition to temperature. For instance, the concentration of various ions in your blood must be kept steady, along with pH and the concentration of glucose.
Regulatory mechanisms have 4 essential features. Name them and gi.pdffootwearpark
Regulatory mechanisms have 4 essential features. Name them and give one example of each
from 2 of the following: drinking, feeding, sleep, circadian rhythms and temperature regulation
Regulatory mechanisms have 4 essential features. Name them and give one example of each
from 2 of the following: drinking, feeding, sleep, circadian rhythms and temperature regulation
Solution
Regulatory mechanisms have 4 essential features:
1. The internal system variable to be regulated (characteristic to be regulated)
2. An optimal value of set point
3. A detector to monitor the variable
4. homoeostatic correctional mechanism
Positive feedback mechanism is defined as the output response produced by the activity of input
signal trough a specific amount of stimulus on the organ during the process of homeostasis.
Positive feedback in isolation is not sufficient to maintain homeostasis because of set point
alterations triggered by the stimulus. Sometimes, if the effect is not going to produce in time
when the stimulus arrived to the organ, homeostasis cannot be reached as it may trigger harmful
effects. This is due to incapability of the organ to maintain the adequate direction of a given
stimulus result in severe acceleration of its effect sometimes finally disequilibrium in
homeostasis. Therefore, homeostasis can be better achieved by negative feedback loop.
1. Temperature regulation- hypothalamus:
Fever mechanism: Initially pyrogens produced by the microbial species either bacteria or viruses
or internal arachidonic acid metabolites such as prostaglandins and prostacyclins promote a
raised \"set point\" on hypothalamus ((detector to monitor the temperature variable) in the brain
followed by peripheral vasoconstriction associated with active generation of heat finally raise in
ambient temperature (detector to monitor the variable). This vasoconstriction (before increasing
temperature of the body) is going to enable reduction of heat loss via skin and makes person to
feel cold.
2. Circadian rhythms:
Circadian rhythms and SCN: Suprachaismatic nuclei (SCN) that is receives inputs from retinas
of the eyes and maintains equilibrium with the daily circadian rhythms. These SCN often
produce neuronal impulses of circadian rhythms. It has clearly observed in hamster due to
increase in circadian periods before surgery procedure and also increased in after surgery
procedure but decreased in t hamster. Thereby it is concluded that SCN controls these rhythms
via feedback loops and via hormones. Even sometimes after removal from brain, SCN produces
impulses. There are “a few other components” outside the SCN that profoundly exhibit circadian
patterns are pituitary body and pineal body in the brain.
Feedback mechanism involves the following events: Cells regulate their metabolic activity
through positive & negative feedback mechanisms in which \"mainly enzymatic protein
synthesis\" mediates regulation of cell metabolic activity. Negative feedback mechanism induce
\"constant\".
Homeostasis| feedback control system - a brief medical study martinshaji
Homeostasis depends on the ability of your body to detect and oppose these changes. Maintenance of homeostasis usually involves negative feedback loops. ... The control center will process the information and activate effectors ..
this study gives a brief introduction about homeostasis
please comment
thank uu
lec 2 Homeostasis and its mechanism with examplesayeshavirk45
In this slide you will find introduction of homeostasis, mechanism of homeostasis, processes involve in homeostasis, nwgative amd positive feedback mechanisms with examples.
GraphSummit Singapore | The Art of the Possible with Graph - Q2 2024Neo4j
Neha Bajwa, Vice President of Product Marketing, Neo4j
Join us as we explore breakthrough innovations enabled by interconnected data and AI. Discover firsthand how organizations use relationships in data to uncover contextual insights and solve our most pressing challenges – from optimizing supply chains, detecting fraud, and improving customer experiences to accelerating drug discoveries.
Climate Impact of Software Testing at Nordic Testing DaysKari Kakkonen
My slides at Nordic Testing Days 6.6.2024
Climate impact / sustainability of software testing discussed on the talk. ICT and testing must carry their part of global responsibility to help with the climat warming. We can minimize the carbon footprint but we can also have a carbon handprint, a positive impact on the climate. Quality characteristics can be added with sustainability, and then measured continuously. Test environments can be used less, and in smaller scale and on demand. Test techniques can be used in optimizing or minimizing number of tests. Test automation can be used to speed up testing.
Dr. Sean Tan, Head of Data Science, Changi Airport Group
Discover how Changi Airport Group (CAG) leverages graph technologies and generative AI to revolutionize their search capabilities. This session delves into the unique search needs of CAG’s diverse passengers and customers, showcasing how graph data structures enhance the accuracy and relevance of AI-generated search results, mitigating the risk of “hallucinations” and improving the overall customer journey.
Pushing the limits of ePRTC: 100ns holdover for 100 daysAdtran
At WSTS 2024, Alon Stern explored the topic of parametric holdover and explained how recent research findings can be implemented in real-world PNT networks to achieve 100 nanoseconds of accuracy for up to 100 days.
Generative AI Deep Dive: Advancing from Proof of Concept to ProductionAggregage
Join Maher Hanafi, VP of Engineering at Betterworks, in this new session where he'll share a practical framework to transform Gen AI prototypes into impactful products! He'll delve into the complexities of data collection and management, model selection and optimization, and ensuring security, scalability, and responsible use.
Unlocking Productivity: Leveraging the Potential of Copilot in Microsoft 365, a presentation by Christoforos Vlachos, Senior Solutions Manager – Modern Workplace, Uni Systems
Removing Uninteresting Bytes in Software FuzzingAftab Hussain
Imagine a world where software fuzzing, the process of mutating bytes in test seeds to uncover hidden and erroneous program behaviors, becomes faster and more effective. A lot depends on the initial seeds, which can significantly dictate the trajectory of a fuzzing campaign, particularly in terms of how long it takes to uncover interesting behaviour in your code. We introduce DIAR, a technique designed to speedup fuzzing campaigns by pinpointing and eliminating those uninteresting bytes in the seeds. Picture this: instead of wasting valuable resources on meaningless mutations in large, bloated seeds, DIAR removes the unnecessary bytes, streamlining the entire process.
In this work, we equipped AFL, a popular fuzzer, with DIAR and examined two critical Linux libraries -- Libxml's xmllint, a tool for parsing xml documents, and Binutil's readelf, an essential debugging and security analysis command-line tool used to display detailed information about ELF (Executable and Linkable Format). Our preliminary results show that AFL+DIAR does not only discover new paths more quickly but also achieves higher coverage overall. This work thus showcases how starting with lean and optimized seeds can lead to faster, more comprehensive fuzzing campaigns -- and DIAR helps you find such seeds.
- These are slides of the talk given at IEEE International Conference on Software Testing Verification and Validation Workshop, ICSTW 2022.
GraphSummit Singapore | The Future of Agility: Supercharging Digital Transfor...Neo4j
Leonard Jayamohan, Partner & Generative AI Lead, Deloitte
This keynote will reveal how Deloitte leverages Neo4j’s graph power for groundbreaking digital twin solutions, achieving a staggering 100x performance boost. Discover the essential role knowledge graphs play in successful generative AI implementations. Plus, get an exclusive look at an innovative Neo4j + Generative AI solution Deloitte is developing in-house.
UiPath Test Automation using UiPath Test Suite series, part 5DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 5. In this session, we will cover CI/CD with devops.
Topics covered:
CI/CD with in UiPath
End-to-end overview of CI/CD pipeline with Azure devops
Speaker:
Lyndsey Byblow, Test Suite Sales Engineer @ UiPath, Inc.
LF Energy Webinar: Electrical Grid Modelling and Simulation Through PowSyBl -...DanBrown980551
Do you want to learn how to model and simulate an electrical network from scratch in under an hour?
Then welcome to this PowSyBl workshop, hosted by Rte, the French Transmission System Operator (TSO)!
During the webinar, you will discover the PowSyBl ecosystem as well as handle and study an electrical network through an interactive Python notebook.
PowSyBl is an open source project hosted by LF Energy, which offers a comprehensive set of features for electrical grid modelling and simulation. Among other advanced features, PowSyBl provides:
- A fully editable and extendable library for grid component modelling;
- Visualization tools to display your network;
- Grid simulation tools, such as power flows, security analyses (with or without remedial actions) and sensitivity analyses;
The framework is mostly written in Java, with a Python binding so that Python developers can access PowSyBl functionalities as well.
What you will learn during the webinar:
- For beginners: discover PowSyBl's functionalities through a quick general presentation and the notebook, without needing any expert coding skills;
- For advanced developers: master the skills to efficiently apply PowSyBl functionalities to your real-world scenarios.
Essentials of Automations: The Art of Triggers and Actions in FMESafe Software
In this second installment of our Essentials of Automations webinar series, we’ll explore the landscape of triggers and actions, guiding you through the nuances of authoring and adapting workspaces for seamless automations. Gain an understanding of the full spectrum of triggers and actions available in FME, empowering you to enhance your workspaces for efficient automation.
We’ll kick things off by showcasing the most commonly used event-based triggers, introducing you to various automation workflows like manual triggers, schedules, directory watchers, and more. Plus, see how these elements play out in real scenarios.
Whether you’re tweaking your current setup or building from the ground up, this session will arm you with the tools and insights needed to transform your FME usage into a powerhouse of productivity. Join us to discover effective strategies that simplify complex processes, enhancing your productivity and transforming your data management practices with FME. Let’s turn complexity into clarity and make your workspaces work wonders!
Essentials of Automations: The Art of Triggers and Actions in FME
Human physiology part 3
1. Human physiology part 3Homeostatic Mechanisms and cellular communication(Chapter 7 vander) John Paul L. Oliveros, MD
2. General Characteristics Homeostasis Denotes the relatively stable conditions of the internal environment Steady State A system in which a particular variable is not changing but energy must be added continuously to maintain this variable constant Setpoint/operating point Steady-state temperature of the thermoregulatory system “Stability of an internal environmental variable is achieved by balancing of inputs and outputs “
3. General Characteristics Negative-feedback system An increase or decrease in the variable regulated brings about responses that tend to move towards the opposite direction of the original change Most common homeostatic mechanisms in the body e.g. Dec in body temp responses to inc body temp to original value
4. General Characteristics Positive-feedback Mechanism Initial disturbance in a system sets off a train of events that increase the disturbance even further Does not favor stability Abruptly displaces a system away from its normal set point e.g. Uterine contractions during labor
5. General Characteristics “Homeostatic control systems do not maintain complete constancy of the internal environment in the face of continued change in the external environment, but can only minimize changes” As long as the initiating event continues, some change in the regulated variable must persists to serve as a signal to maintain to homeostatic response Error signal: persisting signal needed to inform our body that initiating event is still present and that there is still a need to maintain a response Any regulated variable in the body has a narrow range of normal values The range depends on: magnitude of changes in the external conditions Sensitivity of the responding homeostatic system the more precise the regulating system, the smaller the error signal needed, the narrower the variable range
6. General Characteristics Reset of set points The values of that the homeostatic control systems are trying to keep relatively constant can be altered e.g. Fever higher temp is adaptive to fight infection e.g. Decrease serum Iron during infection to deplete infectious organisms of iron required for it to replicate Set points may also change on a rythmical basis Set points may also change due to clashing demands of different regulatory systems
7. General Characteristics Feedforward regulation Frequently used in conjunction with negative-feedback systems Anticipates changes in a regulated variable Improves speed of the body’s homeostatic responses Minimizes fluctuations in the level of the variable regulated Reduces deviation from the set-point. e.g. Skin nerve receptors for temp detects cold weather and activates body’s thermoregulatory systems before actual decrease in body temp
9. Reflexes Reflexes Stimulus response sequence A specific involuntary, unpremeditated, unlearned “built-in” response to a particular stimulus However, it may be learned or acquired, but distinction may not be always clear Reflex arc Pathway mediating a reflex
10. Reflex Arc Components Stimulus Detectable change in the internal or external environment Receptor Detects the environmental change AKA detector Produces a signal in response to a stimulus Afferent pathway Pathway traveled by the signal to the Integrating center Integrating center Receives signals from many receptors responding to different stimuli Integrates numerous bits of information Output of the integrating center reflects the net effect of the total afferent input Efferent pathway The pathway of information from integrating center and effector Effector A device whose change in activity constitutes overall response of the system
12. Reflexes All body cells act as an effector in homeostatic reflex 2 major classes of effector tissues: Muscles glands 2 Reflex systems Nervous system e.g. Thermoregulatory reflex Endocrine system Glands: integrating center receptor Hormones Blood borne chemical messenger May serve as an efferent pathway
13. Local Homeostatic Response Local homeostatic response Another group of biological responses of great importance for homeostasis Initiated by a change in the internal or external environment (stimulus) Induces alteration in cell activity with the net effect of counter acting the stimulus Local response is the result of sequence of events proceeding from a stimulus However, the entire sequence of events occurs only in the area of the stimulus Provide individual areas of the body with mechanisms for local self regulation e.g. Skin damage local cellular release of protective chemicals
14. Intercellular Chemical Messengers Vast majority of communiction between cells is performed by chemical messengers Intercellular communication is essential for reflexes, local homeostatic response and therefore to homeostasis 3 categories of chemical messengers Hormones Neurotransmitters Paracrine agents
15. Intercellular Chemical Messengers Hormone Enables the hormone secreting cell to act on its target cell Delivered by blood Neurotransmitter Chemical messengers secreted by nerve cells Released from nerve cell endings and diffuses into the ECF in between nerves/cells to act upon the 2nd Nerve cell or effector cell Neurohormones Nerve cell secretions that enter the bloodstream to act on cells elsewhere in the body
16. Intercellular Chemical Messengers Paracrine Agents Synthesize by cells and released to the ECF in presence of a stimulus Diffuse into the neighboring target cells Inactivated rapidly by locally existing enzymes Do not enter the blood stream in large quantities Autocrine Agents Chemical secreted by a cell acts on the same cell Frequently, chemical messengers may act as paracrine or autocrine agents Seemingly endless list of paracrine and autocrine agents identified Nitric Oxide Fatty acid derivatives Peptides and AA derivatives Growth factors Etc., etc. Stimuli for release are extremely varried Local chemical changes (e.g change in O2 levels) Neurotransmitters hormones
17. Intercellular Chemical Messengers Eicosanoids Paracrine/autocrine agents that exert a wide variety of effects in virtually every tissue and organ system A family of substances produced from arachidonic acid Polyunsaturated FA Present in PM phospholipids Groups: Cyclic endoperoxides Prostaglandins Thromboxanes leukotrienes
18. Intercellular Chemical Messengers Eicosanoids Beyond Phospholipase A2, the eicosanoid pathway found in a particular cell determine which eicosanoids the cell synthesizes in response to a stimulus Each major eicosanoid subdivision has more than 1 member Structural molecular difference designated by a letter (e.g. PGA, PGE) Further subdivisions by number subscripts (PGE2, PGE3) Once synthesized in response to a stimulus, they are immediately released and act locally Drugs that influence eicosanoid pathway Aspirin: Inhibits cyclooxygenase Blocks the synthesis of endoperoxides, prostaglandins and thromboxanes NSAIDs: Also blocks cyclooxygenase Reduce pain, fever, inflammation Adrenal Steroids: Used in large doses Inhibits phospholipaseA2 Block production of all eioosanoids
19. Processes Related to Homeostasis Acclimatization Biological rhythms Regulated Cell Death: Apoptosis Aging Balance in the homeostasis of chemicals
20. Acclimatization Adaptation: Denotes a characteristic that favors survival in specific environments Homeostatic control systems are inherited biological adaptations Acclimatization: A type of adaptation in which there is an improved functioning of an already existing homeostatic system An individual response to a particular environmental stress is enhanced without a change in genetic endowment Due to prolonged exposure to stress e.g. Sauna bath 1st day : 30 min 1 week : 1-2 hrs/day 8th day: earlier sweating, more profuse sweating, body temp does’t rise as much Usually completely reversible Once stress is removed, body reverts back to preacclimatization condition Developmental acclimatization: Acclimatization is induced early in life (critical period) and becomes irreversible
21. Biological Rhythms Circadian rhythm Most common type Cycles approximately every 24 hrs Body functions Waking and sleeping Body temperature Hormone concentrations Excretion of ions in urine Etc.
22. Biological Rhythms Add another anticipatory component to homeostatic control systems Act as a feed-forward system operating without detectors Enable homeostatic mechanisms to be utilized immediately and automatically activation at times when a challenge is more likely to occur but before it actually does occur e.g. Decrease urinary K+ excretion at night Entrainment: Setting of the actual hours by the body with timing cues provided by environmental factors e.g. Experiment done on chambers with time to ‘lights off” controlled wake-sleep cycled persisted but at 25 hrs cycle (free-running rhythm) Environmental cues: Light-Dark cycle: most important environmental cue External environmental temp Meal timing Many social cues
23. Biological Rhythms Phase shift rhythms Reset of the internal clock by environmental time cues Jet lag Happens when one jets from east or west to a different time zone Sleep-wake cycle and other circadian rhythms slowly shift to the new light-dark cycle Symptoms may be caused by disparity between external time and internal time Symptoms: disruption of sleep, gastrointestinal disturbances, decreased vigilance and attention span, general feeling of malaise
24. Biological Rhythms Neural basis of body rhythms Suprachiasmatic nucleus A collection of nerve cells in the hypothalamus Functions as the principal pacemaker (time clock) for circadian rhythms Probably involves the rhythmical turning on and off of critical genes in the pacemaker cells Input: from eyes and many parts of the nervous system Output: other parts of the brain Pineal Gland: One of the outputs of the pacemaker Secretes melatonin (usually at night)
25. Biological Rhythms Have different effects on the body’s resistance to various stresses and responses to different drugs Heart attack: 2x in the first hours of waking Asthma: usually at night Asthma meds: usually given at night to deliver a high dose of med between 12am-6am
26. Apoptosis Regulated cell death The ability to self-destruct by activation of an intrinsic cell suicide program Important role in the sculpting of a developing organismand in the elimination of undesirable cells (e.g. Cancerous cells) Regulation of the number of cells in tissues and organs Balance between cell proliferation and cell death e.g. Neutrophils die by apoptosis 24 hrs after being produced in the BM
27. Apoptosis Occurs by controlled autodigestion of cell contents Endogenous enzymesbreakdown nucleus and DNA breakdown of organelles Plasma membrane intact to contain cell contents Signal sent to nearby phagocytes eat dying cells Toxic breakdown products are contained no inflammatory response triggered Necrosis: cell death due to injury release of toxic cell contents inflammatory response All cells contain apoptopic enzymes maintained inactive by chemical survival signals sent by neighboring cells, hormones, and extracellular matrix
28. Apoptosis Abnormal inhibition of Apoptosis: cancer Abnormal high rate of apoptosis: degenerative disease (e.g. Osteoporosis)
29. Aging Physiologic manifestations: Gradual detrioration in the function of virtually all tissues and organs systems Deterioration of the homeostatic control systems to respond to environmental stresses Decrease in the number of cells in the body Decreased cell division Increase cell death Malfunction of remaining cells Immediate cause: Interference in the function of the cells macromolecules (e.g. DNA)
30. Aging Decreased cell division Built in limit to the number of times a cell divides DNA loses a portion of its terminal segment (telomere) each time it replicates Genetic and environmental factors Progressive damage Variability of lifespan: 1/3- genes 2/3- differing environments
31. Aging Genes Probably those that code for proteins that regulate the processes of cellular and macromolecular maintenance and repair Werner’s syndrome: premature aging due to a mutation of a single gene that is critical for DNA replication or repair Difficulty in determining if changes in the body are due to aging or disease Can the aging process be inhibited or slowed down? Exerise Balanced diet: reduces formation of free radicals
32. Balance in the Homeostasis of Chemicals Balance diagram for a chemical substance
33. Balance in the Homeostasis of Chemicals Exception to scheme: mineral electrolytes Can’t be synthesized Do not normally enter thru lungs Can’t be removed by metabolism e.g. Na+ Generalizations of the balance concept: During any period of time, total-body balance depends upon the relative rates of net gain and net loss to the body The pool concentration depends not only upon the total amount of the substance in the body, but also upon exchanges of the substance within the body
34. Balance in the Homeostasis of Chemicals 3 states of total-body balance Negative balance: Loss exceeds gain amount of substance in the body is decreasing Positive balance: gain exceeds loss, amount in body increasing Stable balance: gain = loss A stable balance can be upset by alteration of the amount being gained or lost in a single pathway in the schema
35. Section B: Mechanisms by which chemical messengers control cells Homeostatic Mechanisms and Cellular Communication
36. Receptors Chemical Proteins: ligands Receptors: target cell proteins Binding site Glycoproteins located Plasma membrane More common Transmembrane CHONs Has segments extracellular, within the membrane, and intracellular Where lipid-insoluble messengers bind Intracellular Mainly in the nucleus Where lipid soluble chemical messengers bind
37. Receptors Specificity: A very important characteristic of Intercellular communication Cells differ in types of receptors they contain Frequently, just one cell type possesses the receptor required for the combination with a given chemical messenger “superfamilies” : group of receptors closely related structurally for a group of messengers
38. Receptors Different cell types may possess the same receptors for a particular messenger, but responses to the same messenger may differ Receptor functions as a molecular switch that switches on when a messenger binds to it e.g. Norephinephrine Smooth muscle of blood vessel contract Pancreas decrease insulin secretion A single cell may contain several different receptor types for a single messenger Response different from one receptor to another in the same cell e.g. 2 epinephrine receptor sites in smooth muscle cells of BV (contraction vs dilation) The degree to which the molecules of a messenger bind to different receptor sites in a single cel depends on the affinity of the different receptor types for the messenger
39. Receptors A single cell contains many different receptors for different chemical messengers Saturation: response increases as extracellular concentration of the messener increases Upper limit to responsiveness due to finite number of receptors available that become saturated at a point Competition: Ability of different messenger molecules that are very similar in structure to compete with each other for a receptor Antagonist: drugs that bind on the receptors without activatng them prevent messengers from binding and triggering a response e..g. B-blockers
40. Receptors Agonist: Drugs that bind on a particular receptor and trigger the cell’s response as if a true chemical messenger had combined with the receptor e.g. Ephidrine epinephrine receptors Down-regulation: High ECF messenger concentration target cell receptors decrease Reduces target cells’ responsiveness to frequent or intense stimulation by a messenger Local negative feedback mechanism e.g. Insulin glucose uptake decrease insulin receptors Up-regulation: Cells exposed to a prolongd period of very low concentrations of a messenger maydevelop many more receptors for the messenger e.g. Denervated muscls contract when injected with small amounts of neurotransmitter
41. Receptors Down-regulation Binding of messengers to receptors endocytosis degradation of receptors Up-regulation Stores of receptors in IC vessicles insertion via exocytosis Gene that code for receptors Alteration of expression during down/up-regulation Receptors may decrease or increase due to a disease process Myasthenia gavis: aceylcholine receptors in muscles are destroyed mscle weakness/destruction
42. Signal Transduction Pathways The sequences of events between receptor activation and the cell’s response Signal: Receptor activation Transduction: Process in which stimulus is transformed into a response Lipid-soluble messengers: Receptors inside the cell Lipid-insoluble messengers Receptors in the plasma membrane of cell
43. Signal Transduction pathways Receptor activation: Initial step leading to the cell’s ultimate responses to the messenger Causes a change in the conformation of the receptor Common denominator: all directly due to alterations of a particular cell protein Changes may be in the form of: Permeability, transport properties, or electrical state of the plasma membrane The cell’s metabolism The cell’s secretory activity The cell’s rate of proliferation and differentiation Cell’s contractile activity
44. Signal Transduction Pathways Pathways initiated by intracellular pathways Lipid soluble messengers mostly hormones Closely related structurally Receptors Steroid hormone receptor superfamily Intracellular, mostly in the nucleus Inactive when not bound to messenger Activation altered rates og gene transcription Transcription Factor Receptor + Hormone Regulatory protein that directly influences gene transcription Response element: specific sequence near a gene in DNA where the receptor binds Increases the rate of the gene’s transcription into mRNA mRNA direct synthesis of CHON encoded by the gene One gene may be subject to control by a single receptor In some cases, transcription of the gene/s is decreased by the activated receptor
46. Signal Transduction Pathway Pathways initiated by Plasma membrane receptors First messengers Intercellular chemical messenger Hormones, neurotransmitters, paracrine agents Second messengers Non protein substance/enzymatically generated cytoplasmtransmit signals Protein kinase Any enzyme that phosphorylates other CHONs by transfering them a PO4 group from ATP Changes the activity and sonformation of the CHON May involve may CHON kinase
47. Signal Transduction Pathway Receptors that Function as ion channels Receptor constitute an ion channel Activation opening of channels diffusion of specific channels change in membrane potential cell’s response Ca++ channel increase cytostolic Ca++ conc. essential for signal transduction pathways
48. Signal Transduction Pathways Receptors that function as enzymes With intrinsic enzyme activity Almost all are protein-kinases, mostly tyrosine-kinases Binding of messenger change in receptor conformation activation of enzymatic portionautophosphorylation of tyrosine groups phosphotyrosine “docking sites” for other CHONs Cascade of signaling pathways within the cell Guanylyl cyclase receptor: Catalyzes formation of cGMP (2nd messenger) activation of cGMP-dependent protein kinase phosphorylation of a CHON cell’s response
49. Signal Transduction Pathways Receptors that interact with Cytoplasmic JAK Kinases Receptor with intrinsic enzmatic activity Enzymatic activity on receptor’s tyrosine kinase and on separate cytoplasmic kinases (JAK kinases)bound to the receptor Receptor and JAK kinase: function as a unit Messenger receptor activation of JAK kinase phoshorylation of CHONs transcription factors synthesis of new CHONs that mediate cell’s response
50. Signal Transduction Pathways Receptors that interact with G proteins Largest group of receptors G-proteins on the cytoplasm is bound to the receptors Messenger receptor conformational change 1 of 3 subunits of G-proteins link with plasma membrane effector proteins sequence of events cell’s response G-proteins: serve as a switch to couple a receptor with an ion channel or an enzyme in plasma membrane
51. Signal Transduction Pathway Effector Protein Enzymes: Adenylyl cyclase and Cyclic AMP Phospholipase C, diacylglycerol, and Inositol Triphosphate
52. Signal Transduction Pathway Adenylyl cyclase and cyclic AMP Messenger receptor activation of G protein activation of Adenylyl Cyclase conversion of ATP cAMP (2nd messenger) sequence of events cell’s response Phosphodiesterase: enzyme that breaks down cAMP to non cyclic AMP, thus termination of its action cAMP activation cAMP dependent protein kinase (Protein-kinase A) phosphorylation of proteins cell response Amplification: 1 active adenylyl cyclase catalyzation of > 100 cAMP molecules cAMP dependent protein kinase can phosphorylate large number of different proteins exert multiple actions on a cell cAMP dependent protein kinase may inhibit other enzymes
56. SignalTransduction Pathways Phospholipase C, Diacylglycerol, and Inositol Triphosphate Gq phospholipase C breakdown of PIP2 DAG and IP3 different sequence cascade cell response DAG activates protein kinase C phosphorylation of many proteins cell response IP3 enters cytosol binds wiith Ca++ channels in Endoplasmic reticulum opening of Ca++ channels Ca++ diffuses from ER to cytosol increase cytostolic CA++ sequence of events cell response
58. Signal Transduction Pathways Control of ions by G Proteins Direct G-protein gating (fig 7-13d) G-protein interacts directly with ion channels in PM All events occur in the plasma membrane No 2nd messengers involved Indirect G-protein gating (fig 7-17) Utilizes a 2nd messenger
59. Signal Transduction Pathways Ca++ ion as a 2nd messenger Ca++ is maintained extremely low in cytosol Large electrochemical gradient favoring diffusion of Ca++ via channels in both PM and ER Stimulus: change cytostolic Ca++ levels Active transport systems Ion channels Ca++ channels openingChemical stimuliElectrical gradient Ca++ (2nd messenger) bind channels in ER opening of channels release of Ca++ from ER ( calcium-induced calcium release) 2nd messenger IP3 Ca++
60. Signal Transduction Pathways Ca++ ions as 2nd messenger Ca++ can bind with various CHONs Ca++ binding alters CHON conformation and activates their function Calmodulin + Ca++ change in shape activation/inhibition of protein kinases Calmodulin –dependent protein kinase activation/inibition phosphorylation activation/inibition of CHONs cell response
62. Signal Transduction Pathways Receptors and Gene Transcription Plasma membrane receptors: transduction pathways activate Intracellular transcription factors using 2nd messengers Primary Response Genes: Genes with transcription factors activated by first messenger Proteins encoded by PRGs may itself be a transcription factor for another gene
63. Signal Transduction Pathways Cessation of activity in signal transduction Key event: cessation of receptor activation Decrease in the concentration of the first messenger molecules in the region of the receptor Metabolism by enzymes in the vicinity Uptake by adjacent cells Diffusion away Chemical alteration of the receptor (usually by phosphorylation) Lower affinity for the 1st messenger Release of the messenger Removal of plasma membrane receptor and its endocytosis