BSI Lecture 19 Adaptation/Desensitization

Question 1

_____________ is a GPR with a bound light-sensitive messenger.

Answer 1

Rhodopsin

Question 2

Rhodopsin can be excited by as little as one photon and cause the activation of the heterotrimeric G-protein _______.

Answer 2

Transducin (Gt) only found in photoreceptors

Question 3

Adaptation: The effector is a cGMP phosphodiesterase, does it increase or decrease cGMP?

Answer 3

Decrease, which in turn closes an ion channel

Question 4

Adaptation: From 1 rhodopsin to 500 transducins; 10^5 molecules of cGMP, this is an example of ___________

Answer 4

Amplification

Question 5

________ and ______ is a general physiological term used to describe various mechanisms necessary to cope with stimulilsignals that vary widely in strength.

Answer 5

Adaptation; desensitization

Question 6

__________ tends to refer more to actual changes in receptor function whereas __________ can include altered behavior

Answer 6

Desensitization, adaption

Question 7

Adaptation is seen frequently in signal pathways that respond to _______ signals and ______

Answer 7

chemical; light

Question 8

T or F? Desensitization allows cells to respond regardless of “background” levels of stimulation.

Answer 8

False, adaption not desensitization

Question 9

_________ can respond to a few photons on a moonless night or reduce amplification so they still respond in bright sunshine; _______ intracellular Ca2+/Ca2+-dependent kinases causes this negative feedback.

Answer 9

Photoreceptors, increased

Question 10

T or F? Ionotropic receptors can adapt or desensitze to repeated agonist by a “slow” confirmation change in the receptor resulting in abnormally tight binding of the agonist w/o opening the channel.

Answer 10

True

Question 11

What are the 2 principal types of receptor desensitization?

Answer 11

Heterologous, homologous

Question 12

________ desensitization is negative feedback within the same pathway (turning off GPR)

Answer 12

Homologous

Question 13

________ involves negative feedback affecting GPR initiating a different pathway.

Answer 13

Heterologous

Question 14

T or F? Homologous desensitization involves phosphorylation of the GPR by GRK’s.

Answer 14

True

Question 15

T or F? Homologous desensitization involves specific phosphorylation of the GPR but by different serine/threonine kinases at different serine and/or threonine residues.

Answer 15

False, heterologous desensitization

Question 16

_______ desensitization results in loss of G-protein coupling or removal of receptors entirely by endocytosis.

Answer 16

Homologous

Question 17

_______ desensitization results in reduced G-protein coupling.

Answer 17

Heterologous

Question 18

How is heterologous desensitization reversed?

Answer 18

By phosphatases, which restores G-protein coupling

Question 19

T or F? Heterologous feedback mechanism often involves cAMP-dependant protein kinase (PKA) or can be PKC-mediated.

Answer 19

True

Question 20

Ligand-bound form of the GPR is phosphorylated at specific serine/threonine residues and this ________ coupling to the G-protein so it can not be activated.

Answer 20

decrease

Question 21

______ desensitization involves GRK phosphorylating the GPR which then facilitates arrestin binding which makes the GPR unable to activate its G-protein (uncoupled)

Answer 21

Homologous

Question 22

______ desensitization can trigger internalization by endocytosis, the GPR can then be degraded or recycled

Answer 22

Homologous

Question 23

T or F? Arrestin binding can activate MAPK cascade by acting as an “adapter” so recruiting the various kinases to the membrane.

Answer 23

True. ( Has been most studied for teh Beta2-adrenergic receptor, its GRK is known as BetaARK and its arrestin is Beta-Arrestin)

Question 24

T or F? G-protein effector can be switch from one type of G-protien to another by being phosphorylated.

Answer 24

True. This in turn can change the response (ie switching Gs (increase cAMP) to Gi (reducing cAMP))

Question 25

T or F? GPR’s under constant agonist application will have a constant increase cell response.

Answer 25

False, there is an initial rapid decrease in response.

Question 26

T or F? Initial response to constant agonist involves no change in receptor density.

Answer 26

True

Question 27

Response to constant agonist slowly declines further due to a ______ in _____ _______

Answer 27

decrease ; receptor density (this is due to internalization)