10 - GPCR 2 Flashcards
What do GPCR actions depend on
Pattern of expression
What is an example of GPCR expression pattern
mu-opioid receptor distribution in spinal cord where pain transmission neurons are located but not where non-noxious transmission neurons are
What does increased ligand-receptor affinity do
Improve signal detection
Affect time of action
What affinity do hormones acting on GPCR have
Very high affinity
Low concentrations are used to signal
Are GPCR actions considered fast or slow when compared to ionotropic receptors
Slow (Fastest: 50ms lag 100ms action)
Synaptic (1 ms)
What else modifies the rate of signalling
Number of receptors
How does intrinsic efficacy influence response at GPCR
Higher intrinsic efficacy = increased receptor response
Methadone > Morphine > Buprenorphine
What are some GPCR regulation processes to reduce effective receptor number or signalling efficacy
1) Phosphorylation
2) GRK and Arrestin binding = < coupling
3) Endocytosis = < R
What are two effects of GPCR desensitisation and tolerance
Desensitisation and tolerance
GPCRs can signal from (2)
Cell surface
Endosomes
Are closely related GPCRs hard to discriminate pharmacologically
Yes
Do D2 or D3 receptors appear to mediate worse side effects
D2
What are D2/D3 dopamine receptor antagonists
Antipsychotics
What does the structure of D3R bound to eticlopride suggest
Selectivity can be deeloped
Which category of drug selectivity for GPCR appears to have less side effects
Category C
