Biological relevance of pituitary adenylate cyclase-activating polypeptide(PACAP) in the gastrointestinal tract

Since its initial discovery in 1989, pituitary adenylate cyclase activating peptide (PACAP) has been noted to distribute widely in the brain, the resp iratory and the gastrointestinal system. It occurs in two bioactive molecul es, PACAP-27 and the C-terminally extended PACAP-38, which evoke activity b y binding to three distinct types of high-affinity, G-protein coupled membr ane receptors. It is present throughout the entirety of the gut but is rare in certain areas such as the intestinal mucosa and islets of Langerhans. P ACAP-induced biological effects are protean and include alterations of moti lity in the bowel and the gallbladder, stimulation of gastric acid and inte stinal secretion, hormone/enzyme release from the exocrine and endocrine pa ncreas, and the induction as well as inhibition of proliferation in neuroen docrine cells and tumors. Its hepatic activity has to date not been elucida ted in detail. One of the interesting features of PACAP is the species and organ dependent variation of its biological effects. Of particular note is its superior potency when compared with other neuropeptides identified in t he gut, and the involvement of a number of different second messenger syste ms upon PACAP receptor activation. (C) 1999 Elsevier Science B.V. All right s reserved.