What is the first intracellular effect when an opioid binds to its receptor?

What is the first intracellular effect when an opioid binds to its receptor?

• A. Decreased adenylate cyclase activity leading to decreased cAMP
• B. Increased adenylate cyclase activity
• C. Increased calcium influx
• D. Increased cAMP

Answer: (A)

Opioids bind to their GPCR, which is coupled to the Gi/o protein. The immediate intracellular event is activation of this Gi/o, where the Gαi subunit inhibits adenylate cyclase. This lowers the conversion of ATP to cAMP, so intracellular cAMP levels fall and protein kinase A activity decreases. This reduction in cAMP is a primary signaling step that helps dampen neuronal activity and transmitter release. Additionally, Gβγ subunits can further modulate the cell by opening GIRK channels and inhibiting voltage-gated calcium channels, reinforcing the decrease in neurotransmitter release. So the first intracellular effect is a decrease in adenylate cyclase activity leading to reduced cAMP.

Opioids bind to their GPCR, which is coupled to the Gi/o protein. The immediate intracellular event is activation of this Gi/o, where the Gαi subunit inhibits adenylate cyclase. This lowers the conversion of ATP to cAMP, so intracellular cAMP levels fall and protein kinase A activity decreases. This reduction in cAMP is a primary signaling step that helps dampen neuronal activity and transmitter release. Additionally, Gβγ subunits can further modulate the cell by opening GIRK channels and inhibiting voltage-gated calcium channels, reinforcing the decrease in neurotransmitter release. So the first intracellular effect is a decrease in adenylate cyclase activity leading to reduced cAMP.