BSI Lecture 19 Adaptation/Desensitization Flashcards
_____________ is a GPR with a bound light-sensitive messenger.
Rhodopsin
Rhodopsin can be excited by as little as one photon and cause the activation of the heterotrimeric G-protein _______.
Transducin (Gt) only found in photoreceptors
Adaptation: The effector is a cGMP phosphodiesterase, does it increase or decrease cGMP?
Decrease, which in turn closes an ion channel
Adaptation: From 1 rhodopsin to 500 transducins; 10^5 molecules of cGMP, this is an example of ___________
Amplification
________ and ______ is a general physiological term used to describe various mechanisms necessary to cope with stimulilsignals that vary widely in strength.
Adaptation; desensitization
__________ tends to refer more to actual changes in receptor function whereas __________ can include altered behavior
Desensitization, adaption
Adaptation is seen frequently in signal pathways that respond to _______ signals and ______
chemical; light
T or F? Desensitization allows cells to respond regardless of “background” levels of stimulation.
False, adaption not desensitization
_________ 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.
Photoreceptors, increased
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.
True
What are the 2 principal types of receptor desensitization?
Heterologous, homologous
________ desensitization is negative feedback within the same pathway (turning off GPR)
Homologous
________ involves negative feedback affecting GPR initiating a different pathway.
Heterologous
T or F? Homologous desensitization involves phosphorylation of the GPR by GRK’s.
True
T or F? Homologous desensitization involves specific phosphorylation of the GPR but by different serine/threonine kinases at different serine and/or threonine residues.
False, heterologous desensitization
_______ desensitization results in loss of G-protein coupling or removal of receptors entirely by endocytosis.
Homologous
_______ desensitization results in reduced G-protein coupling.
Heterologous
How is heterologous desensitization reversed?
By phosphatases, which restores G-protein coupling
T or F? Heterologous feedback mechanism often involves cAMP-dependant protein kinase (PKA) or can be PKC-mediated.
True
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.
decrease
______ desensitization involves GRK phosphorylating the GPR which then facilitates arrestin binding which makes the GPR unable to activate its G-protein (uncoupled)
Homologous
______ desensitization can trigger internalization by endocytosis, the GPR can then be degraded or recycled
Homologous
T or F? Arrestin binding can activate MAPK cascade by acting as an “adapter” so recruiting the various kinases to the membrane.
True. ( Has been most studied for teh Beta2-adrenergic receptor, its GRK is known as BetaARK and its arrestin is Beta-Arrestin)
T or F? G-protein effector can be switch from one type of G-protien to another by being phosphorylated.
True. This in turn can change the response (ie switching Gs (increase cAMP) to Gi (reducing cAMP))
T or F? GPR’s under constant agonist application will have a constant increase cell response.
False, there is an initial rapid decrease in response.
T or F? Initial response to constant agonist involves no change in receptor density.
True
Response to constant agonist slowly declines further due to a ______ in _____ _______
decrease ; receptor density (this is due to internalization)
