GPCR's reguleren de activiteit van adenylylcyclase

When GPCRs bind ligands such as glucagon or epinephrine , the  stimulatory G proteins get activated and, in turn, activate the membrane-bound enzyme adenylyl cyclase.

The activated enzyme converts ATP to a second messenger cyclic AMP that uses downstream kinases such as protein kinase A  or PKA to regulate the metabolism of fats and sugars.

Prolonged exposure to a high concentration of ligands induces GPCR phosphorylation by PKA. Receptor phosphorylation blocks the binding of additional G_s and inhibits adenylyl cyclase activation, preventing GPCR overstimulation.

Binding of hormones such as prostaglandin E₁ or adenosine to GPCRs activates inhibitory G proteins.

The activated G_ɑi dissociates from GPCR, binds, and inhibits adenylyl cyclase, preventing cyclic AMP synthesis.