pituitary adenylate cyclase-activating polypeptide-27

**Pituitary adenylate cyclase-activating polypeptide-27 (PACAP27)** is a 27-amino acid neuropeptide that corresponds to the N-terminal 27 residues of PACAP38. It is one of two functional isoforms of pituitary adenylate cyclase-activating polypeptide (PACAP), with PACAP38 being the more predominant form in most brain regions. PACAP27 binds with high affinity to the pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1) and vasoactive intestinal peptide receptors (VPAC1 and VPAC2). It strongly stimulates cyclic AMP (cAMP) accumulation, with studies showing up to 60-fold increases with an EC50 value of 0.067 nM in certain cell types. The peptide is involved in various physiological processes, including neuronal signaling, blood vessel dilation, pain pathways, and immune system modulation. Recent clinical research has demonstrated that PACAP27 can provoke migraine-like attacks in migraine patients, strengthening the understanding of PACAP's role in migraine pathogenesis.