Receptors

Question 1

Define: Receptor

Answer 1

the component of the organism with which the chemical agent is presumed to interact

Question 2

What are a majority of receptors composed of?

Answer 2

proteins

Question 3

What are proteins composed of?

Answer 3

amino acids connected by peptide bonds

Question 4

Describe: Intracellular receptors

Answer 4

lipid-soluble ligand that crosses the membrane and acts on receptor within the cell

Question 5

Describe: Tyrosine Kinase receptors

Answer 5

transmembrane receptor where the ligand binds extracellularly and stimulates intracellular protein tyrosine kinase

Question 6

Describe: Ion Channel receptors

Answer 6

ligand binds which induces opening or closing of ion channels

Question 7

Describe: G-protein receptors

Answer 7

transmembrane receptor protein that stimulates G-protein which triggers production of an intracellular second messenger

Question 8

What type of receptor are Nicotinic Acetylcholine (ACh) receptors?

Answer 8

ligand gated ion channel

Question 9

Describe: Nicotinic ACh receptor structure

Answer 9

transmembrane receptors composed of 5 subunits: alpha(2x), beta, gamma, delta- ligand binding site on the alpha units

Question 10

What ligands can bind to Nicotinic Acetylcholine (ACh) receptors?

Answer 10

acetylcholine, epibatidine (poisonous tree frog), alpha-bungarotoxin (snake venom)

Question 11

What ligands presented in lecture are nAChR agonists?

Answer 11

acetylcholine and epibatidine (poisonous tree frog)

Question 12

What ligands presented in the lecture are nAChR antagonists?

Answer 12

alpha-bungarotoxin (snake venom)

Question 13

Briefly describe the events directly following activation of Nicotinic Acetylcholine (NACh) receptors.

Answer 13

agonist binding causes the ion channel to open allowing sodium(Na+) to flow down the concentration gradient (into the cell)- which produces a localized excitatory postsynaptic potential (depolarization)

Question 14

Describe: Voltage-gated ion channel

Answer 14

ligands do not bind directly to the channel, but are triggered by membrane potential- once the membrane potential depolarizes over a certain threshold triggering additional sodium (Na+) channels to open, which allows more Na+ to enter the cell that initiates the action potential

Question 15

How can drugs target voltage-gated ion channel?

Answer 15

drugs can bind to the “voltage sensor” domain

Question 16

Describe: Epibatidine (poisonous tree frog)

Answer 16

nicotinic AChR agonist w/ high affinity (activates the receptor) resulting in muscle spasms and eventually paralysis

Question 17

Describe: alpha-Bungarotoxin (snake venom)

Answer 17

nicotinic AChR antagonist (blocks the receptor) resulting in paralysis due to poor muscle contraction

Question 18

Describe: Tetrodotoxin (puffer fish)

Answer 18

blocks voltage-gated sodium (Na+) channels resulting in paralysis and eventually death

Question 19

What type of receptor are Muscarinic receptors?

Answer 19

G protein-coupled receptors

Question 20

What type of receptor are Adrenergic receptors?

Answer 20

G protein-coupled receptors

Question 21

Describe: G protein-coupled receptor structure

Answer 21

transmembrane receptor that contains an alpha, beta, and gamma subunit with GDP(inactive)/GTP(active) in complex with the alpha subunit intracellularly

Question 22

Briefly describe the actions following G protein receptor activation.

Answer 22

ligand binds extracellularly acts by increasing intracellular intracellular second messenger concentration

Question 23

Name and briefly describe the different families of Galpha proteins.

Answer 23

-Gs = stimulates cyclic AMP production
-Gi = inhibits cyclic AMP production
-Gq = activates phospholipase C, increase intracellular calcium (Ca2+)
-G12/13 = promotes growth and differentiation

Question 24

Describe: Pertussis toxin (whooping cough)

Answer 24

locks Gi proteins in a GDP bound state (inactive) thus allowing cyclic AMP to continued to be produced

Question 25

Describe: Cholera toxin

Answer 25

locks Gs proteins in a active state thus resulting in overproduction of cAMP -> stimulating PKA -> stimulates Cl- channel activity = high concentration of Cl- in the intestinal lumen causing diarrhea and severe hydration

Question 26

What G protein receptors have alpha subunit Gq?

Answer 26

muscarinic receptor (M1, M3, M5) and adrenergic receptor (a1)

Question 27

Describe the Mechanism: G protein Gq

Answer 27

activate phospholipase C to hydrolyze PIP2 (second messenger -> increase of IP3 -> increase cytoplasmic Ca2+ ->increase diacylglycerol, increase PKC

Question 28

What G protein receptors have alpha subunit Gi?

Answer 28

muscarinic receptor (M2, M4) and adrenergic receptor (a2)

Question 29

Describe the Mechanism: G protein Gi

Answer 29

decreased adenylyl cyclase (ATP enzyme) and decreased cAMP

Question 30

What G protein receptors have alpha subunit Gs?

Answer 30

adrenergic receptor (b1, b2, b3)

Question 31

Describe the Mechanism: G protein Gs

Answer 31

increase adenylyl cyclase (ATP enzyme), increase cAMP, increase PKA resulting in protein phosphorylation

Question 32

What happens when there are multiple signals acting on the same cell?

Answer 32

net results = intergrated effects

Question 33

How can receptors be regulated?

Answer 33

desensitization, internalization, degradation

Question 34

Describe the Mechanism: Desensitization

Answer 34

-agonist binds and activates the G protein -G protein-coupled receptor kinase (GRK) phosphorylate the active receptor which prevents receptor interaction with Gs and promotes binding to a different protein, beta arrestin to the receptor -the receptor-arrestin complex binds to coated pits, promoting receptor internalization -dissociation of agonist from the internalized receptor reduces beta arrestin binding affinity, allowing dephosphorylation of receptors by phosphatase -depending, once the agonist concentration is achieved in the endosome, a second phase of G protein activation can occur internally before receptors recycle to the plasma membrane -recycling of receptors serves to "resensitize" cellular response by restoring functional receptors to the cell surface, where they will interact with the agonist again (conditions may effect the efficiency and rate) -in general, repeated or prolonged agonist exposure favors the delivery of internalized receptor to lysosomes rather than recycle to cell surface.