GPCRs 2 Flashcards
What are some agonists of the mu-opioid receptors?
Morphine, met-enkephalin and DAMGO.
How do the responses of the mu-opioid agonists vary?
DAMGO and met-enkephalin are full agonists, morphine is a partial agonist.
Why is DAMGOs potency higher than morphine?
It has a greater efficacy (not affinity - all three agonists bind similarly)
How does the desensitization of the mu-opioid receptors vary for their different agonists?
DAMGO and met-enkephalin have desensitization within 5 minutes whereas morphine shows no desensitization.
What is the effect of activating PKC on the effect of morphine?
It induces morphine desensitization.
What effect does GRK2 have at receptors?
It causes DAMGO-induced desensitization but not morphine-induced desensitization.
What role does arrestin have with DAMGO and morphine?
DAMGO causes arrestin translocation, but not morphine.
What is the mechanism involved in morphine desensitization if it doesn’t involve arrestin?
PKC - two separate mechanisms for densensitization even though they activate the same receptor.
What is functional selectivity?
Biased agonism - different agonists acting at the same receptor can have different actions.
What is the mechanism behind functional selectivity?
The idea that different agonists stabilise different conformational changes - can bind and stabilise the active or inactive conformation. The idea that receptors are constantly changing conformation and the binding of an agonist just stabilises a certain conformation, rather than activating them.
How does functional selectivity explain that two different agonists can cause desensitization by different mechanisms?
There must be more than one active conformational state.
What can the concept of multiple conformational states affect?
How agonists cause receptor desensitization, arrestin-based signalling, the G-protein activated by an agonist.
