The document discusses three main types of receptors: ligand-gated receptors, enzyme-linked receptors, and nuclear receptors. Ligand-gated receptors include nicotinic acetylcholine receptors and GABAA receptors, which act as ion channels and mediate fast synaptic transmission. Enzyme-linked receptors include tyrosine kinase receptors, JAK/STAT receptors, Toll-like receptors, and guanylyl cyclase receptors, which activate intracellular enzyme pathways to regulate processes like cell growth and inflammation. Nuclear receptors directly bind to DNA and act as transcription factors to regulate gene expression, responding to ligands like steroids, vitamins, and fatty acids.
This presentation impart a knowledge about Histamine,receptor,and antagonist.
Recent advances also mentioned like H3 & H4 receptors role in cognitive impairment etc.
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The JAK-STAT signalling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through a process called transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), Signal Transducer and Activator of Transcription proteins (STATs), and receptors (which bind the chemical signals).[1] Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.
This presentation impart a knowledge about Histamine,receptor,and antagonist.
Recent advances also mentioned like H3 & H4 receptors role in cognitive impairment etc.
Jump to search
The JAK-STAT signalling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through a process called transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), Signal Transducer and Activator of Transcription proteins (STATs), and receptors (which bind the chemical signals).[1] Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.
These are intracellular (cytoplasmic or
nuclear) soluble proteins which respond to
lipid soluble chemical messengers that penetrate
the cell (Fig. 4.10). The receptor protein (specific for each hormone/regulator) is inherently
capable of binding to specific genes, but its
attached proteins HSP-90 and may be some
others prevent it from adopting the configuration needed for binding to DNA. When the
hormone binds near the carboxy terminus of
the receptor, the restricting proteins (HSP-90,
etc.) are released, the receptor dimerizes and
the DNA binding regulatory segment located
in the middle of the molecule folds into the
functionally active configuration. The liganded
receptor dimer moves to the nucleus and binds
other co-activator/co-repressor proteins which
have a modulatory influence on its capacity to
alter gene function. The whole complex then
attaches to specific DNA sequences (hormone
response elements) of the target genes and
facilitates or represses their expression so
that specific mRNA is synthesized/repressed
on the template of the gene. This mRNA
moves to the ribosomes and directs synthesis
of specific proteins which regulate activity of
the target cells.
All steroidal hormones (glucocorticoids,
mineralocorticoids, androgens, estrogens,
progesterone), thyroxine, vit D and vit A function in this manner. Different steroidal hormones affect different target cells and produce
different effects because each one binds to its
own receptor and directs a unique pattern of
synthesis of specific proteins. The specificity as
to which hormone will be bound is provided
by the hormone binding domain, while that as
to which gene will be activated or repressed
is a function of the DNA binding/N-terminus
domain. Different ligands of the same nuclear
receptor have been found to induce ligand-specific
conformations of the receptor so that different
combinations of co-activators and co-repressors
may be bound in different target tissues, e.g.
selective estrogen receptor modulators (SERMs)
tamoxifen and raloxifene have differing patterns
of action on various estrogenic target organs.
Chimeric receptors have also been produced
which respond to one hormone, but produce
the effects of the other hormone.
This transduction mechanism is the slowest in its time course of action (takes hours)
because the adequate quantity of the effector protein
will have to be produced before the response
occurs. The effects also generally out last
the signal (hormone), because the majority of the
generated effector proteins have slow turnover,
and persist in the body even after the hormone
has been eliminated.
Neurotransmitters/General aspect and steps involved in neurotransmission.pptxSIRAJUDDIN MOLLA
Neurotransmission (Latin: transmission "passage, crossing" from transmitter "send, let through"), is the process by which signalling molecules called neurotransmitters are released by the axon terminal of a neuron and bind to and react with the receptors on the dendrites of another neuron
Neurotransmission (Latin: transmission "passage, crossing" from transmitter "send, let through"), is the process by which signalling molecules called neurotransmitters are released by the axon terminal of a neuron and bind to and react with the receptors on the dendrites of another neuron
These are intracellular (cytoplasmic or
nuclear) soluble proteins which respond to
lipid soluble chemical messengers that penetrate
the cell (Fig. 4.10). The receptor protein (specific for each hormone/regulator) is inherently
capable of binding to specific genes, but its
attached proteins HSP-90 and may be some
others prevent it from adopting the configuration needed for binding to DNA. When the
hormone binds near the carboxy terminus of
the receptor, the restricting proteins (HSP-90,
etc.) are released, the receptor dimerizes and
the DNA binding regulatory segment located
in the middle of the molecule folds into the
functionally active configuration. The liganded
receptor dimer moves to the nucleus and binds
other co-activator/co-repressor proteins which
have a modulatory influence on its capacity to
alter gene function. The whole complex then
attaches to specific DNA sequences (hormone
response elements) of the target genes and
facilitates or represses their expression so
that specific mRNA is synthesized/repressed
on the template of the gene. This mRNA
moves to the ribosomes and directs synthesis
of specific proteins which regulate activity of
the target cells.
All steroidal hormones (glucocorticoids,
mineralocorticoids, androgens, estrogens,
progesterone), thyroxine, vit D and vit A function in this manner. Different steroidal hormones affect different target cells and produce
different effects because each one binds to its
own receptor and directs a unique pattern of
synthesis of specific proteins. The specificity as
to which hormone will be bound is provided
by the hormone binding domain, while that as
to which gene will be activated or repressed
is a function of the DNA binding/N-terminus
domain. Different ligands of the same nuclear
receptor have been found to induce ligand-specific
conformations of the receptor so that different
combinations of co-activators and co-repressors
may be bound in different target tissues, e.g.
selective estrogen receptor modulators (SERMs)
tamoxifen and raloxifene have differing patterns
of action on various estrogenic target organs.
Chimeric receptors have also been produced
which respond to one hormone, but produce
the effects of the other hormone.
This transduction mechanism is the slowest in its time course of action (takes hours)
because the adequate quantity of the effector protein
will have to be produced before the response
occurs. The effects also generally out last
the signal (hormone), because the majority of the
generated effector proteins have slow turnover,
and persist in the body even after the hormone
has been eliminated.
Neurotransmitters/General aspect and steps involved in neurotransmission.pptxSIRAJUDDIN MOLLA
Neurotransmission (Latin: transmission "passage, crossing" from transmitter "send, let through"), is the process by which signalling molecules called neurotransmitters are released by the axon terminal of a neuron and bind to and react with the receptors on the dendrites of another neuron
Neurotransmission (Latin: transmission "passage, crossing" from transmitter "send, let through"), is the process by which signalling molecules called neurotransmitters are released by the axon terminal of a neuron and bind to and react with the receptors on the dendrites of another neuron
The signal transduction pathway uses a network of interactions within cells, among cells, and throughout plant.
The external signals that affect plant growth and development include many aspects of the plant’s physical, chemical, and biological environments. Some external signals come from other plants.
Many signals interact cooperatively and synergistically with each other to produce the final response. Signal combinations that induce such complex plant responses include red and blue light, gravity and light, growth regulators and mineral nutrients .
For example the overall regulation of seed germination involves control by both external factors and internal signals.
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.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
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2. LIGAND-GATED ION CHANNELS
• Ionotropic receptors.
• Nervous system
-excitatory ( Ach , glutamate)
- inhibitory( glycine or GABA)
• Fast synaptic transmission
• E.g. - Nicotinic Acetylcholine receptor at NM junction.
- GABAA receptor
3. Molecular structure
• Commonest- heteromeric assemblies of 4 or 5 subunits
e.g. -Pentameric – nAchr
-Tetrameric –NMDA
• Transmembrane helices arranged around a central aqueous
channel.
18. Receptor serine/threonine kinases-
• Analogous to the receptor tyrosine kinases
• Phosphorylation of serine and/or threonine
• The activated receptor , phosphorylates SMAD
• e.g. TGF-β
19. MECHANISM OF ACTION
Agonist binding
Dimerization of receptor
Phosphorylation of kinase
Phosphorylation of SMAD
Gene transcription
20. CLINICAL SIGNIFICANCE
Under trial (phase 3)
SELUMETINIB -differentiated thyroid cancer
-K-Ras protein mutated non-small cell lung cancer.
21. Toll-Like Receptors-
• Signaling related to the innate immune system.
• Highly expressed in hematopoietic cells.
• Ligands - pathogen products (lipids, peptidoglycans, lipopeptides)
and viruses.
• Activation of these receptors produces an inflammatory responses
22. MECHANISM OF ACTION
Ligand-induced dimerization
MAL/MyD88 recruitment ( IRAKs autophosphorylation)
TRAF6 activation
Interaction with TAB1 and TAK1
Phosphorylation of the NF-κB Transcription
28. Nuclear receptors-
• NRs can directly interact with DNA - “ ligand activated transcription
factors”.
• These transduce signals by modifying gene transcription.
• E.g. glucocorticoids, mineralocorticoids, Vit D and A
30. TYPES OF NUCLEAR RECEPTOR
CLASS 1 CLASS 2
Location Cytosolic Nuclear
Ligand binding Homodimers Heterodimers often with RXR
Mechanism of action Translocation to nucleus.
Binding to HREs
Complexed with co-repressors,
which are displaced following
ligand binding, allowing the
binding of trans activators
E.G. Estrogen ( Er α)
Glucocorticoid( GRα )
Retinoid X (RXR α,β,γ)
Thyroid hormone (TR α,β )
Ligand binding and channel opening occur on a millisecond timescale. Major ligand-gated channels in the nervous system are those that respond to excitatory neurotransmitters such as ACh or glutamate and inhibitory neurotransmitters such as glycine or GABA . Ligand (Latin: ligare—to bind) Any molecule which attaches selectively to particular receptors or sites
There are several structural families, the commonest being heteromeric assemblies of four or five subunits, with transmembrane helices arranged around a central aqueous channel. nAChR, nicotinic acetylcholine receptor, NMDA, N-methyl-D-aspartic acid receptor
consists of a pentameric assembly of different subunits, of which there are four types, termed α, β, γ and δ, each of molecular weight (Mr) 40–58 kDa
They are activated by a wide variety of protein mediators, including growth factors and cytokines and hormones such as insulin and leptin. They have large extracellular ligand binding domain connected through a single transmembrane helical peptide chain to an intracellular subunit having enzymatic property in the cytosolic phase.
1-they incorporate tyrosine kinase in their intracellular domain. Cytokine receptors. These receptors (Fig. 3.17B) lack intrinsic enzyme activity. When occupied, they activate various tyrosine kinases, such as Jak (the Janus kinase).
With the exception of the insulin receptor, which has α and β chains (see Chapter 47), these macromolecules consist of single polypeptide chains with large, cysteine-rich extracellular domains, short transmembrane domains, and an intracellular region containing one or two protein tyrosine kinase domains. Activation of growth factor receptors leads to cell survival, cell proliferation, and differentiation. Activation of the ephrin receptors leads to neuronal angiogenesis, axonal migration, and guidance
The first step following agonist binding is dimerisation, which leads to autophosphorylation of the intracellular domain of each receptor. SH2-domain proteins then bind to the phosphorylated receptor and are themselves phosphorylated.
Ras –GTP ase family RAF proto-oncogene serine/threonine-protein kinase Growth factor receptor-bound protein 2
BCR-ABL is a constitutively activated tyrosine kinase that is associated with chronic myeloid leukemia
oral tyrosine kinase inhibitor that acts upon vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR
The intracellular domain binds a separate, intracellular tryosine kinase termed a Janus kinase (JAK). • JAKs phosphorylate other proteins termed signal transducers and activators of transcription (STATs).
Jak/Stat pathway (Fig. 3.17B) is involved in responses to many cytokines. Dimerisation of these receptors occurs when the cytokine binds, and this attracts a cytosolic tyrosine kinase unit (Jak) to associate with, and phosphorylate, the receptor dimer. Jaks belong to a family of proteins, different members having specificity for different cytokine receptors. Among the targets for phosphorylation by Jak are a family of transcription factors (Stats). These are SH2-domain proteins that bind to the phosphotyrosine groups on the receptor–Jak complex, and are themselves phosphorylated. Thus activated, Stat migrates to the nucleus and activates gene expression
analogous to the receptor tyrosine kinases except that they have a serine-threonine kinase domain in the cytoplasmic region of the protein
Gene regulatory protein smad
Transforming growth factor beta receptors
Samd proteins are transcription protiens
The orally administered drug has dual specificity for mitogen-activated protein kinase inhibitors
AstraZeneca plc
TLR DOMAIN- toll/interleukin-1 domain
Myeloid differentiation primary response 88 (MYD88
Myelin and lymphocyte protein is a protein that in humans is encoded by the MAL gene
Interleukin-1 receptor-associated kinase 1
TNF receptor associated factor (TRAF)
TGF-beta activated kinase 1 (MAP3K7) binding protein 1
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1
nuclear factor kappa-light-chain-enhancer of activated B cells
T-cell development, maturation, and proliferation.[4
B-type natriuretic peptide, a hormone secreted by the ventricles in response to volume overload, acts via a receptor guanylyl cyclase
Nesiritide (Natrecor) is the recombinant form of the 32 amino acid human B-type natriuretic peptide, which is normally produced by the ventricular myocardium. Nesiritide works to facilitate cardiovascular fluid homeostasis through counterregulation of the renin–angiotensin–aldosterone system, stimulating cyclic guanosine monophosphate, leading to smooth muscle cell relaxation.
Cyclic GMP signaling pathways. Formation of cGMP is regulated by cell surface receptors with intrinsic GC activity and by soluble forms of GC. The cell surface receptors respond to natriuretic peptides such as ANP with an increase in cGMP. sGC responds to NO generated from l-arginine by NOS. Cellular effects of cGMP are carried out by PKG and cGMP-regulated PDEs. In this diagram, NO is produced by a Ca2+/calmodulin–dependent NOS in an adjacent endothelial cell
protein kinase G phosphodiesterase enzyme
First cloned receptor –retinoid x receptor ( vitamin A derivative 9-cisretinoic acid )
AF1 - binds cell specific transcription factors Core domain - DNA recognition and binding Zinc finger – hormone response elements in gene
cysteine- (or cystine-/histidine-) rich loops in the amino acid chain that are held in a particular conformation by zinc ions
C-terminal domain- ligand binding domain
Hinge region – receptor dimerization
HRE – short sequence of DNA that is able to attach to a hormone receptor complex
transactivate or transrepress genes by binding to ‘positive’ or ‘negative’ HREs
Class II NRs are generally bound to co-repressor proteins
NRs almost always operate as heterodimers together with the retinoid X receptor (RXR).
