Central effects of pituitary adenylate cyclase activating polypeptide (PACAP) on gastric motility and emptying in rats.

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a new member of the secretin-glucagon-vasoactive intestinal peptide (VIP) peptide family. PACAP is widely distributed not only in the mammalian brain but also in the gastrointestinal tract. Here, we investigated the effects of central and peripheral administrations of PACAP on gastric motility and gastric emptying in rats. We found that the intracerebroventricular or intracisternal injection of PACAP increased gastric motility in a dose-dependent manner. The intracisternal injection of PACAP delayed gastric emptying. These central effects of PACAP on gastric motility and emptying were blocked by bilateral vagotomy. In contrast, intravenous administration of PACAP decreased gastric motility and delayed gastric emptying. The peripheral inhibitory effect was unaffected by bilateral vagotomy, adrenalectomy, phentolamine, and propranolol. We investigated the effect of PACAP38 on blood glucose levels (BGL) at the same doses as those used in the gastric motility and emptying studies in urethane-anesthetized rats. The intravenous but not intracerebroventricular injection of PACAP38 (1-8 nmol/rat) produced a significant increase in the BGL. We conclude that PACAP has opposite central and peripheral effects on gastric motility, ie, central PACAP activates the vagal pathway in the central nervous system to increase gastric motility, whereas peripheral PACAP inhibits gastric motility via an unknown pathway. The delay in gastric emptying after the central administration of PACAP might be due to the lack of coordinated gastropyloroduodenal contraction, whereas that after the peripheral administration might be due to the inhibition of gastric contraction, and this effect may be related to the hyperglycemic action of PACAP.