Modulation of signaling Flashcards
Can one activated Beta-adrenergic receptor activate more than 1 Gs protein?
Yes, and each Gs many stimulate many adenylyl cyclase to form 10,000 cAMP molecules
One cAMP molecule activates one PKA molecule. The protein kinase A molecule then phosphorylates 100 proteins. What is this an example of?
Amplification
What are the 2 factors of agonist potency?
Level of affinity
Level of ability to signal and elicit a response
What is the EC50?
The agonist concentration that gives half of the max response
What is potency measured by?
EC50
What is efficacy measured by?
Level of signaling and response
What is the difference between a full agonist and a partial agonist?
A full agonist elicits the highest possible response compared to other agonists
Partial agonist elicits a smaller maximal reponse compared to full agonists
What are competitive antagonists?
Competitive antagonists bind to the receptor instead of agonists
Do competitive antagonists elicit a response?
No
Can a maximum agonistic effect still be attained in the presence of a competitive antagonist?
Yes, if enough agonists are present
What effect do competitive antagonists have on the agonist concentration response curve?
Shifted to the right (requires more agonist)
What is a non-competitive antagonist?
Binds to an alternative site to down-regulate the receptor response
Can a maximum agonistic effect still be achieved with the presence of a non-competitive antagonist?
No
What is cooperativity?
2 molecules are necessary for a steep response curve
What causes all or nothing responses?
Need for cooperativity
What is attenuation?
Reduction of agonist concentrations to levels that do not produce a detectable response
How is attenuation accomplished?
Dilution
Re-uptake
Enzymatic degradation
Name an example of agonist re-uptake
Specific transporters take dopamine, NE, glutamate, GABA back in to signaling cell
What does cocaine block?
Re-uptake of neurotransmitters
Name 2 enzymes that degrade agonists
acetycholinesterase
neuropeptidases
Describe attenuation by G-protein receptors
Norepinephrine leaves receptor
Gs-alpha subunit hydrolyzes GTP to GDP
Phosphodiesterase breaks down cAMP
Phosphatases dephosphorylate proteins
What are the types of attenuation?
desensitization
internalization
down-regulation
What can lead to the desensitization of receptors?
Long duration of agonist stimulation
Describe the receptor desensitization pathway
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
Why does internalization of receptors lead to a lessened response?
Less receptors are present in the membrane to elicit response
Describe the 2 pathways of resensitization
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
