Modulation of Cell Signaling

Question 1

Example of amplification in β1-adrenergic receptor

Answer 1

1. 1 β1-adrenergic receptor may activate many G(s)
2. Each G(s) may stimulate AC to form many cAMPs
3. 1 cAMP may activate 1 PKA to phosphorylate many proteins

And now you have a shitload of proteins from one receptor being stimulated!

Question 2

2 ways agonists differ

Answer 2

1. Affinity for receptor

2. Ability to initiate signaling and elicit response

Question 3

Agonist potency is due to?

Answer 3

1. High affinity

2. High ability to signal and elicit response

Question 4

Potency definition

Answer 4

Ranking of agonists according to EC(50)

Question 5

Efficacy definition

Answer 5

Ranking of agonists according to magnitude of maximal effect

Question 6

Full agonists

Answer 6

Agonists with most efficacy (largest maximal response)

Question 7

Partial agonists

Answer 7

Agonists with some efficacy (smaller maximal response)

Question 8

Antagonists

Answer 8

Bind to receptor but do not cause a response

Question 9

Agonists

Answer 9

Bind receptor and cause response

Question 10

Competitive antagonists

Answer 10

Bind to receptor, competing with agonists

Question 11

Competitive antagonists shift the dose-response curve to the?

Answer 11

Right

Question 12

How does agonist surmount inhibition by competitive antagonist?

Answer 12

Increase amount of agonist

Question 13

Non-competitive antagonists have what effect on the dose-response relationship?

Answer 13

Reduce maximal effect (not surmountable by agonist)

Question 14

Example of cooperativity

Answer 14

Pregnancy

Question 15

Cooperativity leads to?

Answer 15

“All or nothing” response

Question 16

More partners necessary in a cooperative relationship does what to dose-response relationship curve?

Answer 16

Makes it steeper

Question 17

Ligand definition

Answer 17

Substance which binds to receptor

Question 18

Agonist definition

Answer 18

Substance which binds to receptor and activates cell signaling mechanism

Question 19

EC(50) definition

Answer 19

Concentration of agonist which causes half-maximal effect

Question 20

Attenuation is necessary to prevent?

Answer 20

Uncontrolled signaling

Question 21

Goal of attenuation by agonist removal

Answer 21

Reduction of agonist concentrations to levels which do not produce detectale response

Question 22

3 methods of attenuation by agonist removal

Answer 22

1. Dilution
2. Re-uptake
3. Enzymatic degradation

Question 23

Examples of re-uptake attenuation

Answer 23

1. Specific transporters for norepinephrine and dopamine (can be blocked by cocaine)
2. Glutamate
3. GABA

Question 24

Examples of attenuation via enzymatic degradation

Answer 24

1. Acetylcholinesterase

2. Neuropeptidase

Question 25

Methods of attenuation

Answer 25

1. Agonist removal
2. G-protein hydrolysis
3. Second messenger degradation
4. Target protein dephosphorylation
5. Receptor desensitization/internalization/down-regulation

Question 26

How is attentuation of G-protein receptor initiated?

Answer 26

Agonist-bound receptor is phosphorylated by GRK

Question 27

GRK stands for?

Answer 27

G-protein-receptor-kinase

Question 28

Phosphorylation of agonist-bound receptor does what?

Answer 28

Uncouples G-protein from receptor and permits bind of β-arrestin

Question 29

What happens once phosphorylated receptor has been couple with β-arrestin?

Answer 29

Internalized by endocytosis with helper molecule clathrin

Question 30

How does internalizing receptor by endocytosis inactivate it?

Answer 30

No longer accessible for water-soluble agonists

Question 31

Big idea of attenuation by receptor

Answer 31

Move it from membrane into endosome → can’t be accessed to less response

Question 32

2 ways receptors are resensitized?

Answer 32

1. Recycled into membrane

2. Degraded into lysozymes → new receptors stored in Golgi are sent to membrane