PACAP Regulation of Gastrointestinal Function and Obesity

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a 27- or 38-amino acid peptide that is widely distributed in both the peripheral and central nervous systems. PACAP has been found to be expressed within the enteric nervous system and gastric mucosa and has profound physiological effects in the gastrointestinal tract. We have previously shown that PACAP regulates gastric acid secretion by activating its high affinity PAC1 receptors expressed on gastric enterochromaffin-like cells (ECL). However, the peripheral mechanisms involved in PACAP regulation of appetite and feeding are unknown. Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide abundantly expressed in the central nervous system as well as in the gastrointestinal tract, where it regulates different physiological functions. VIP inhibits gastric acid secretion via its VPAC1 receptors expressed on gastric D cells. VIP also regulates intestinal motility and VIP gene deletion results in the development of intestinal ileus. VIP is involved in the control of appetite/satiety, feeding behavior and in the secretion of some key regulatory metabolic hormones. VIP plays a very important role in the regulation of body weight and mass composition by significantly enhancing body weight and fat mass. Therefore, both PACAP and VIP neuropeptides could be crucial targets for the regulation of appetite/satiety, body phenotype and for the treatment of obesity.