Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38)

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) is a neuropeptide composed of 38 amino acids and is the predominant biological form in mammals, accounting for about 90% of PACAP activity[3][5]. PACAP-38 belongs to the vasoactive intestinal peptide (VIP)/secretin/glucagon superfamily and is highly conserved across species[3]. It functions as a neurotransmitter, neuromodulator, and hormone, with roles in the central and peripheral nervous systems, endocrine system, immune modulation, and reproductive functions[1][5][7]. PACAP-38 exerts many of its biological effects through G protein-coupled receptors, especially the PAC1, VPAC1, and VPAC2 receptors, leading to increased cyclic AMP levels[5]. It has been implicated as a key mediator in the pathophysiology of migraine and headache, where it can induce migraine-like attacks and is a current target for monoclonal antibody therapies in clinical trials[2][4][6][8]. PACAP-38 is also studied for its roles in metabolic and reproductive physiology and investigated as a candidate biomarker in various fluids[1][7].

Other names

PACAP38PACAP (when context refers specifically to the 38-amino acid form)Pituitary adenylate cyclase-activating polypeptide (PACAP; generic, but PACAP-38 is the predominant form)

Monoclonal antibodies inhibit PACAP-38 binding to its receptors, thereby blocking downstream signaling pathways including vasodilation and neurogenic inflammation that are implicated in migraine and headache disorders[2][6][8].