Receptor mechanism

Question 1

What are the 4 classifications of receptor families?

Answer 1

-Ligand gated receptors
-G-protein coupled receptors
-Tyrosine kinase receptors
-Intracellular receptors

Question 2

What is the ligand gated receptor composed of and what do they form?

Answer 2

-Ligand gating receptors composed of 5 protein subunits
-Subunits form an ion channel

Question 3

Where is the ligand binding site located in ligand gated receptors?

Answer 3

-Ligand-binding site on N-terminal region(Extracellular site)

Question 4

What is the signal transduction mechanism in ligand gated receptors?

Answer 4

-Ligand binds to receptor
-Conformational change in subunits
-Ion channel opens
-Increase ion influx
-Change in cell excitability

Question 5

How fast is the response in ligand gated receptors?

Answer 5

-Very fast response as its essential for fast communication

Question 6

What is the structure of G-protein coupled receptors?

Answer 6

-1 single protein
-7 transmembrane regions

Question 7

What is the signal transduction mechanism for G-protein coupled receptors?

Answer 7

-Ligand binds to receptor
-Activation of G proteins
-Production of intracellular messengers
-Cellular function

Question 8

Speed of response for G-protein coupled receptor

Answer 8

-Slower response than ligand gated receptors: seconds to minutes
-During exercise, heart rate increases to provide more blood flow to working muscles

Question 9

What are G proteins?

Answer 9

G proteins are guanine nucleotide binding proteins(GTP/GDP) composed of 3 subunits- alpha, beta and gamma

Question 10

Why is amplification of G proteins signal possible?

Answer 10

-There are a lot more G proteins than receptors and this allows amplification of signal

Question 11

What are the different types of Galpha subunits?

Answer 11

-Different subtypes of alpha subunits e.g. Galphas, Glphai, Galphaq

Question 12

What is the Galphas mediated pathway?

Answer 12

-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

Question 13

What is the Galphai mediated pathway?

Answer 13

-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

Question 14

What is the the Galphaq mediated pathway?

Answer 14

-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

Question 15

What is the structure of tyrosine kinase receptors?

Answer 15

-Monomer-1 single protein subunit-1 transmembrane domain
-N terminal extracellular-binds ligand
-C-terminal intracellular-bind effector

Question 16

What is the signal transduction mechanism of tyrosine kinase receptors?

Answer 16

-Ligand binding to monomers induces dimerization
-Monomers phosphorylate tyrosine residue in each another
-Phosphorylated intracellular domains bind cellular proteins
-Cellular function

Question 17

Example of Inulin and Tyrosine kinase receptor

Answer 17

-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

Question 18

Where are intracellular receptors found?

Answer 18

-Receptor found within cytoplasm of cell

Question 19

What is the structure of an intracellular receptor?

Answer 19

-Monomer-1 single protein subunit
-DNA binding site
-N terminal-binds heat shock protein(HSP) and agonist
-C terminal-control transcription

Question 20

What is the signal transduction method of intracellular receptors?

Answer 20

-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

Question 21

What is the speed like for intracellular receptors?

Answer 21

-This is a very slow response: hours, days, months and beyond

Question 22

What is the cellular mechanism of steroids (Glucocorticoid receptor)?

Answer 22

-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