Modulation of signaling

Question 1

Can one activated Beta-adrenergic receptor activate more than 1 Gs protein?

Answer 1

Yes, and each Gs many stimulate many adenylyl cyclase to form 10,000 cAMP molecules

Question 2

One cAMP molecule activates one PKA molecule. The protein kinase A molecule then phosphorylates 100 proteins. What is this an example of?

Answer 2

Amplification

Question 3

What are the 2 factors of agonist potency?

Answer 3

Level of affinity

Level of ability to signal and elicit a response

Question 4

What is the EC50?

Answer 4

The agonist concentration that gives half of the max response

Question 5

What is potency measured by?

Answer 5

EC50

Question 6

What is efficacy measured by?

Answer 6

Level of signaling and response

Question 7

What is the difference between a full agonist and a partial agonist?

Answer 7

A full agonist elicits the highest possible response compared to other agonists

Partial agonist elicits a smaller maximal reponse compared to full agonists

Question 8

What are competitive antagonists?

Answer 8

Competitive antagonists bind to the receptor instead of agonists

Question 9

Do competitive antagonists elicit a response?

Answer 9

No

Question 10

Can a maximum agonistic effect still be attained in the presence of a competitive antagonist?

Answer 10

Yes, if enough agonists are present

Question 11

What effect do competitive antagonists have on the agonist concentration response curve?

Answer 11

Shifted to the right (requires more agonist)

Question 12

What is a non-competitive antagonist?

Answer 12

Binds to an alternative site to down-regulate the receptor response

Question 13

Can a maximum agonistic effect still be achieved with the presence of a non-competitive antagonist?

Answer 13

No

Question 14

What is cooperativity?

Answer 14

2 molecules are necessary for a steep response curve

Question 15

What causes all or nothing responses?

Answer 15

Need for cooperativity

Question 16

What is attenuation?

Answer 16

Reduction of agonist concentrations to levels that do not produce a detectable response

Question 17

How is attenuation accomplished?

Answer 17

Dilution
Re-uptake
Enzymatic degradation

Question 18

Name an example of agonist re-uptake

Answer 18

Specific transporters take dopamine, NE, glutamate, GABA back in to signaling cell

Question 19

What does cocaine block?

Answer 19

Re-uptake of neurotransmitters

Question 20

Name 2 enzymes that degrade agonists

Answer 20

acetycholinesterase

neuropeptidases

Question 21

Describe attenuation by G-protein receptors

Answer 21

Norepinephrine leaves receptor

Gs-alpha subunit hydrolyzes GTP to GDP

Phosphodiesterase breaks down cAMP

Phosphatases dephosphorylate proteins

Question 22

What are the types of attenuation?

Answer 22

desensitization
internalization
down-regulation

Question 23

What can lead to the desensitization of receptors?

Answer 23

Long duration of agonist stimulation

Question 24

Describe the receptor desensitization pathway

Answer 24

Agonist binds receptor

Receptor is phosphorylated by G-protein-Receptor kinase

Phosphorylation uncouples the G-protein from the receptor and allows Beta-arrestin to bind

Phosphorylated Beta-arrestin receptor is internalized to endosome using Clathrin

Inside endosome, agonist is removed, Beta-arrestin is removed, and receptor is dephosphorylated

Question 25

Why does internalization of receptors lead to a lessened response?

Answer 25

Less receptors are present in the membrane to elicit response

Question 26

Describe the 2 pathways of resensitization

Answer 26

Receptor is recycled back in to the membrane

or

Receptor is degraded in lysosomes and sent to Golgi apparatus to make new receptors for membrane