Receptor mechanism Flashcards
What are the 4 classifications of receptor families?
-Ligand gated receptors
-G-protein coupled receptors
-Tyrosine kinase receptors
-Intracellular receptors
What is the ligand gated receptor composed of and what do they form?
-Ligand gating receptors composed of 5 protein subunits
-Subunits form an ion channel
Where is the ligand binding site located in ligand gated receptors?
-Ligand-binding site on N-terminal region(Extracellular site)
What is the signal transduction mechanism in ligand gated receptors?
-Ligand binds to receptor
-Conformational change in subunits
-Ion channel opens
-Increase ion influx
-Change in cell excitability
How fast is the response in ligand gated receptors?
-Very fast response as its essential for fast communication
What is the structure of G-protein coupled receptors?
-1 single protein
-7 transmembrane regions
What is the signal transduction mechanism for G-protein coupled receptors?
-Ligand binds to receptor
-Activation of G proteins
-Production of intracellular messengers
-Cellular function
Speed of response for G-protein coupled receptor
-Slower response than ligand gated receptors: seconds to minutes
-During exercise, heart rate increases to provide more blood flow to working muscles
What are G proteins?
G proteins are guanine nucleotide binding proteins(GTP/GDP) composed of 3 subunits- alpha, beta and gamma
Why is amplification of G proteins signal possible?
-There are a lot more G proteins than receptors and this allows amplification of signal
What are the different types of Galpha subunits?
-Different subtypes of alpha subunits e.g. Galphas, Glphai, Galphaq
What is the Galphas mediated pathway?
-For example beta adrenoceptors in heart
-one the GPCR is activated, the Galphas subunit will stimulate adenylate cyclase(AC) which increase cAMP levels. This stimulates protein kinase A which causes an increase in heart rate
What is the Galphai mediated pathway?
-For example, acetylcholine at muscaranic2 receptors in heart
-Once the GPCR is activated, the Galphai subunit will inhibit adenylate cyclase(AC) which reduces cAMP levels and inhibits protein kinase A(PKA). This inhibits heart rate
What is the the Galphaq mediated pathway?
-for example, noradrenaline at alpha adrenoceptors or acetylcholine at muscaranic3 receptors
-Once the GPCR is activated, Galphaq activity alongside phospholipase C activity will give rise to cAMP, DAG and IP3 which are termed intracellular messengers
-The DAG will go on to give rise to PKC which is key In cellular events
-IP3 stimulates its receptor which is a calcium ion channel located in the endoplasmic reticulum
-Increase in cytosolic concentration of Ca2+
-Biological response include
-Contraction of smooth muscle in eye, GI tract, blood vessels and airways
What is the structure of tyrosine kinase receptors?
-Monomer-1 single protein subunit-1 transmembrane domain
-N terminal extracellular-binds ligand
-C-terminal intracellular-bind effector
What is the signal transduction mechanism of tyrosine kinase receptors?
-Ligand binding to monomers induces dimerization
-Monomers phosphorylate tyrosine residue in each another
-Phosphorylated intracellular domains bind cellular proteins
-Cellular function
Example of Inulin and Tyrosine kinase receptor
-Example is when insulin bind to insulin receptors and this increases number of GLUT transporters on cell surface which leads to increase glucose uptake from blood plasma into cells
Where are intracellular receptors found?
-Receptor found within cytoplasm of cell
What is the structure of an intracellular receptor?
-Monomer-1 single protein subunit
-DNA binding site
-N terminal-binds heat shock protein(HSP) and agonist
-C terminal-control transcription
What is the signal transduction method of intracellular receptors?
-The drug crosses plasma membrane
-Hormone displaces HSP and binds to the N terminal
-Hormone/receptor complex enters nucleus and binds to hormone-responsive-element on a gene
-This alters gene transcription
What is the speed like for intracellular receptors?
-This is a very slow response: hours, days, months and beyond
What is the cellular mechanism of steroids (Glucocorticoid receptor)?
-Corticosteroid such as dexamethasone crosses the plasma membrane
-Corticosteroid binds to receptor(GCR) and dissociates heat shock protein(HSP)
-Corticosteroid/GCR complex translocates to nucleus
-The expression of genes can be either increased or decreased
