Extracellular Signalling - Receptors Flashcards
How is the specificity of hormonal action achieved?
Through interaction with its complementary receptor
How can different cells respond differently to the same hormone?
There are multiple receptor subtypes within their own transduction mechanisms
What is effect of adrenaline in:
- Muscle and liver
- Adipose tissue
- Cardiomyoctyes
- Stimulates breakdown of glycogen
- Stimulates fatty acid production in adipose tissue
- Increased heart rate and blood pressure by stimulating vascular smooth muscle cells
What are the 4 main classes of receptors?
- Ligand-gated ion channel (ionotropic receptors)
- G-protein coupled receptor
- Receptor tyrosine kinase
- Nuclear hormone receptor
What receptors are cell surface receptors?
- Ligand-gated ion channel
- G protein-coupled receptor
- Receptor tyrosine kinase
What receptors are intracellular receptors?
Nuclear hormone receptor
What signalling molecules are cell surface receptors for?
Hydrophilic signalling molecules
What are signalling molecules are intracellular receptors for?
Lipid-based (lipophilic/hydrophobic) signalling molecules
Describe opening of ligand-gated ion channels
Open and close in response to shift in membrane potential
- Binding causes conformational change in the channel protein allowing the opening of ion channels
- Specific ions (Na+, K+, Ca2+) flow through channel (in or out)
- Alters cells electric potential (membrane potential)
What do ligand-gated ion channels allow?
Rapid synaptic signalling between electrically excitable cells
What type of receptor is nAChR?
Ligand-gated ion channel (ionotropic receptor)
How is nAChR activated?
There are 2 binding sites and both must be occupied for the receptor to become activated
How does nAChR cause membrane depolarisation?
Increased Na+ and K+ permeability –> Na+ moves in and K+ moves out of cell
What is the Renin-Angiotensin System stimulated by?
Decrease in blood pressure / blood Na+ or blood volume
What are the 2 main enzymes involved in the RAS?
Renin and angiotensin-converting enzyme (ACE)
How does decrease in blood pressure affect RAS?
- Decrease in blood pressure detected by kidneys
- Causes release of renin cleaves angiotensin I from N-terminus of angiotensinogen via the liver
- ACE cleaves angiotensin II from angiotensin I
- Angiotensin II causes secretion of aldosterone from adrenal cortex
- Aldosterone has role in water reabsorption and decreases during volume –> increases blood pressure
What type of receptors are Ang II?
GPCRs –> AT1 and AT2
What effects are mediated by AT1 receptor activation?
- Vasoconstriction
- Increased noradrenaline release from sympathetic nerve terminals
- Aldosterone secretion from adrenal cortex
- Vascular growth
What effects are mediated by AT2 receptor activation?
Anti-hypertrophic and anti-hypertensive effects (AT2 receptor activation opposes the effects of AT1 receptor activation)
Does AT1 or AT2 have a higher affinity for Ang II?
Similar affinity but only share 30% sequence identity
What are catalytic receptors?
Receptor itself is an enzyme
What are examples of catalytic receptors?
- Tyrosine kinase receptors
- Serine/Threonine kinase receptors
- cGMP-linked receptors
How do non-catalytic receptors act?
Through cytoplasmic tyrosine kinases
What are examples of non-catalytic receptors?
- Cytokines
- Growth hormone
- Prolactin
What are tyrosine kinase receptors activated by?
Insulin and growth factors
What is effect of kinase-linked receptors?
Act by indirectly regulating gene transcription
What is function of nuclear hormone receptors?
Regulate gene transcription
What is structure of nuclear hormone receptors?
Monomeric structure - separate ligand and DNA-binding domains
How do hormones interact with nuclear hormone receptors?
- Hormones diffuse across plasma membrane and interact with intracellular receptors
- Form hormone-receptor complexes
- Bind to regions of DNA (‘hormone responsive elements’) and affect gene transcription
What are the 2 classes of intracellular receptors?
- Cytosolic (steroid)
2. Nuclear (thyroid)
What are the targets of G protein-coupled receptors (GPCRs)?
Peptide hormones, neurotransmitters
How do G-protein receptors work?
- Binding of ligand results in conformational change of receptor
- Facilitates interaction with signal-transducing heterotrimeric G-protein
- In turn, modulates the activation or inhibition of downstream effector proteins
- These effector proteins modulate the levels of 2nd messenger molecules
What are 2nd messengers?
A small intracellular molecule formed transiently in response to receptor activation e.g. cAMP, cGMP, IP3, DAG and Ca2+
How do AT1 receptor antagonists work?
Bind selectively to AT1- receptors and thus inhibit the effects of angiotensin II
How do aldosterone receptor antagonists work?
Blocks the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy for the management of chronic heart failure
How do ACE inhibitors work?
Prevent production of angiotensin II
As a result, blood vessels enlarge or dilate, and blood pressure is reduced. This lower blood pressure makes it easier for the heart to pump blood and can improve the function of a failing heart.
Used to treat high blood pressure and heart failure
