1. Second messengers are small intracellular molecules that transmit signals within cells after extracellular signaling molecules (hormones or neurotransmitters) bind to cell surface receptors.
2. There are three main types of second messenger systems: cyclic AMP (cAMP), cyclic GMP (cGMP), and inositol trisphosphate (IP3)/diacylglycerol (DAG). These systems activate protein kinases or trigger the release of calcium ions to produce a physiological response.
3. Second messengers amplify and diversify extracellular signals, allowing for precise regulation of multiple cellular processes. Their roles are important for understanding cell signaling, disease mechanisms, and potential drug targets.
MAPK Signaling pathway (Mitogen-activated protein kinase), how the pathway helps in regulation of mitosis, It's activation and inactivation inside the cell, roles of MAPK pathway in cancerous cell, different classes of MAP kinase in human
Introduction
Definition
History
Basic element in signal transduction
Basic Pathway of signal transduction
Types of signal transduction
Second messenger
Pathway of signal transduction
Conclusion
References
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
MAPK Signaling pathway (Mitogen-activated protein kinase), how the pathway helps in regulation of mitosis, It's activation and inactivation inside the cell, roles of MAPK pathway in cancerous cell, different classes of MAP kinase in human
Introduction
Definition
History
Basic element in signal transduction
Basic Pathway of signal transduction
Types of signal transduction
Second messenger
Pathway of signal transduction
Conclusion
References
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
Signal transducing machinery as targets for potential drugs.
Drugs:-
a). Diclofenac- for treating cholera toxin
b). Fasentin- for treating insulin signalling
Cell signaling / Signal Transduction / Transmembrane signaling.
It is the process by which cells communicate with their environment and respond to external stimuli.
When a signaling molecule(ligand) binds to its receptor, it alters the shape or activity of the receptor, triggering a change inside of the cell such as alteration in the activity of a gene / cell division. Thus the original Intercellular Signal is converted into an Intracellular Signal that triggers as a response.
This Slide gives you a idea about the subject Cellular and Molecular pharmacology where the cell signalling, secondary messengers and its intracellular signalling pathways has been celarly explained
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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5. INTRODUCTION
• Cell to cell communication
• Chemical and physical messengers interact with receptors in
the plasma membrane , cytoplasm or nucleus.
• A series of signaling events that mediate the response to each
stimulus.
• Response – specific, amplified ,tightly regulated and
coordinated.
8. • Signaling pathways are characterized by:
1. Multiple, hierarchical steps
2. Amplification of the hormone-receptor binding event which
magnifies the response
3. Activation of multiple pathways and regulation of multiple
cellular functions
4. Feedback mechanisms – tight regulatory control
10. • cAMP pathway
• cGMP pathway
• IP3 / DAG pathway
• Calcium as a second messenger
• Eicosanoids
Second Messengers
11. 11
Second Messengers
• General characteristics
– Low amounts in resting state
– Regulated synthesis
– Regulated destruction
– Act through other proteins
14. cAMP-dependent Protein Kinase A
C
R R
C
+ 4 cAMP
C
C R
R
cAMP
cAMP
cAMP
cAMP
+
The catalytic subunit is
now free to attack a
protein target.
cAMP pathway
15. Active
phosphorylase
Kinase
Inactive
Phosphorylase
Kinase
P
P
Catalytic site
Calmodulin
2ATP 2ADP
cAPK
Kinase enzymes are the targets for the catalytic subunit of PKA
These target enzymes have some unique features.
Phosphorylase kinase, for example, is composed of 4 different subunits .
The delta subunit is calmodulin, a calcium binding protein, that regulates the activity.
The gamma subunit has the catalytic site . The enzyme is not active.
To activate phosphorylase kinase, the catalytic subunit of protein kinase A transfers 2
PO4s from 2 ATPs to the alpha and beta subunits. Phosphorylation at these sites renders
phosphorylase kinase active. Conversely, removing phosphate inactivates the kinase.
16. P
The target kinases phosphorylate enzymes that control critical steps in a pathway.
For example, phosphorylase or glycogen synthase are targets of protein kinase.
For phosphorylase, the kinase enzyme is phosphorylase kinase.
The sequence of events is highlighted in the figure below
Adenylcyclase
C C
R R
cAMP dependent
protein kinase
Phosphorylase
kinase Phosphorylase
Thus hormones(external to the cell) have profound effect on glycogen degradation,
glycogen synthesis, and other processes by controlling the enzyme activities by the
presence or absence of phosphate groups.
P
cAMP pathway
18. • In addition to signaling in the cytoplasm, the catalytic subunit
of PKA can enter the nucleus of cells and phosphorylate and
activate the transcription factor cAMP response element
binding (CREB) protein.
• Phospho-CREB protein increases the transcription of many
genes
• Indirect effect of cAMP mediated by PKA
cAMP pathway
24. Nitric oxide (NO)
NO, a simple gas, is able to diffuse across the membrane, and alters the
activity of intracellular target enzymes. It’s extremely unstable, so its effects are
local. Ex. It signals the dilation of blood vessels.
Mechanism.
Acetylcholine is released from the terminus of nerve cell in the blood
vessel wall. The endothelial cells are stimulated to produce NO (from arginine),
which causes an increased synthesis of cGMP, a second messenger responsible for
blood vessel dilation.
Ach
Nerve cell endothelial cell
NO cGMP Vessel dilationAchR
cGMP Pathway
25. IP3 /DAG
LIGAND RECEPTOR
↓
G protein
↓
Phospholipase C
↓
PIP2 IP3 + DAG
↓
Endoplasmic reticulum opening of Ca channels
↓
Ca++
↓
Protein kinase C Effects
26. G protein
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein-coupled
receptor
Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Ca2
GTP
Figure 11.14-1
27. Figure 11.14-2
G protein
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein-coupled
receptor
Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Ca2
(second
messenger)
Ca2
GTP
28. Figure 11.14-3
G protein
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein-coupled
receptor
Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Various
proteins
activated
Cellular
responses
Ca2
(second
messenger)
Ca2
GTP
30. 30
• Inositol tri-phosphate
• Hydrophilic
• Agonist for internal
calcium channel
• [Ca++]i rises
• Multiple effects through
Ca++-binding proteins
• Diacylglycerol
• Hydrophobic
• Targets PKC (a kinase)
• PKC requires Ca++ and
DAG
IP3 /DAG
31. • Classical PKC family members (PKCα,PKCβ,PKCγ) require
both Ca2+ & DAG for activation.
• The novel PKCs (PKCδ,PKCε,PKCη) are independent of Ca2+
IP3 /DAG
33. • Calcium ions - once they enter the cytoplasm exert allosteric
regulatory effects on many enzymes and proteins.
• Calcium acts as a second messenger by indirect signal
transduction pathways such as via G protein-coupled
receptors.
Calcium as a 2nd Messenger
34. • Low cytoplasmic Ca++ at rest (10–100 nM).
• To maintain this low concentration, Ca2+ is actively pumped from
the cytosol to the extracellular space and into the endoplasmic
reticulum (ER)
• Certain proteins of the cytoplasm and organelles act as buffers by
binding Ca2+.
• Signaling occurs when the cell is stimulated to release calcium ions
(Ca2+) from intracellular stores, and/or when calcium enters the cell
through plasma membrane ion channels.
Calcium as a 2nd Messenger
35. • sudden increase in the cytoplasmic Ca2+ level up to 500–1,000
nM by opening channels in the endoplasmic reticulum or
the plasma membrane.
• Phospholipase C pathway – IP3 & DAG
• Eicosanoids
Calcium as a 2nd Messenger
36. • Many of Ca2+-mediated events occur when the released
Ca2+ binds to and activates the regulatory protein calmodulin.
• Calmodulin may activate calcium-calmodulin-
dependent protein kinases, or may act directly on other
effector proteins.
• Besides calmodulin, there are many other Ca2+-binding
proteins such as troponin C that mediate the biological effects
of Ca2+.
Calcium as a 2nd Messenger
39. This class of lipids act as signaling molecules that bind to cell surface
molecules.
They include: PROSTAGLANDINS
PROSTACYCLIN
TROMBOXANES
LEUKOTRIENES.
The eicosanoids are rapidly broken down and therefore act in autocrine or
paracrine pathways. They stimulate a variety of responses in their target
cells, including blood platelet aggregation, inflammation, and smooth muscle
contraction.
EICOSANOIDS
44. • McCune-Albright syndrome
- A somatic mutation that constitutively activates the Gαs in a mosaic
pattern
- Excess cAMP
- Characteristic triad
i. Variable hyperfunction of multiple endocrine glands, including
precocious puberty in girls
ii. Bone lesions
iii. Pigmented skin lesions (café au lait spots)
Applied
45. Huntington’s disease
• Disturbance of CREB protein in the brain can contribute to the
development and progression of Huntington’s disease.
• Autopsied brains of those who had Huntington's disease have
been found to have incredibly reduced amounts of CREB
protein
Applied
47. Huntington’s disease
• Mutant Htt→ IP3 receptors more sensitive to IP3 → increased
release of Ca2+ from ER→increase in cytosolic and
mitochondrial concentration of calcium→ Ca2+ induced
degeneration of GABAergic medium spiny neurons
Alzheimer's Disease
• Familial – mutation of PS1,PS2,APP genes →increased IP3
mediated calcium release
Applied
48. Eicosanoids are synthesized from arachidonic acid. The first enzyme involved
in their synthesis (cyclooxygenase, COX) is the target of ASPIRIN.
Aspirin actions:
-reduces inflammation and pain (inhibition of prostaglandins)
- reduces platelet aggregation and blood clotting (thromboxanes)
Applications:
- prevention of stroke
AA
COX aspirin
P
T
Applied