When adenylyl cyclase is activated, it catalyzes the conversion of ATP to cyclic AMP (cAMP) and pyrophosphate. This activation primarily occurs through the binding of the Gαs subunit of heterotrimeric G proteins to adenylyl cyclase, which happens after a ligand binds to a G protein-coupled receptor (GPCR) on the cell membrane. The GPCR activation causes the exchange of GDP for GTP on the Gαs subunit, leading to its activation and subsequent stimulation of adenylyl cyclase. The produced cAMP then acts as a second messenger to regulate various cellular processes. Furthermore, regulation of adenylyl cyclase can be complex, with multiple isoforms responding differently to calcium ions, calmodulin, and inhibitory G proteins. Some isoforms are also directly stimulated by molecules like forskolin. In neurons, calcium-sensitive adenylyl cyclases are strategically located to respond quickly to calcium influx and may play roles in learning processes by acting as coincidence detectors activated only by multiple signals together. Thus, adenylyl cyclase activation links extracellular signals received by membrane receptors to intracellular cAMP production and downstream signaling pathways.