Category: signaling
Cyclic AMP is the canonical Gs-coupled second messenger. Adenylate cyclase converts ATP → cAMP on Gs activation; cAMP activates PKA (protein kinase A) → phosphorylates downstream targets (CREB transcription factor, voltage-gated Ca²⁺ channels, ion pumps, contractile proteins, lipases). cAMP is degraded by phosphodiesterases (PDE1-11 isoforms): PDE3 in cardiac + smooth muscle (cilostazol target); PDE4 in inflammatory cells (apremilast, roflumilast targets); PDE5 in vascular + cavernosal smooth muscle (own pathway pde5_no_cgmp_axis — cGMP-specific). Many Rx classes converge here as Gs-coupled receptor agonists: β-agonists, glucagon, GLP-1 agonists, PTH analogs (intermittent pulse), calcitonin, V2 vasopressin. Caffeine + theophylline raise cAMP indirectly via non-selective PDE inhibition + adenosine antagonism. This integrative pathway is mostly for pathway-convergence detection — "any Gs-coupled or PDE-modulating drug" pile-on shows up here.