Pituitary adenylate cyclase activating polypeptides, PACAP‐27 and PACAP‐38: stimulators of electrogenic ion secretion in the rat small intestine

Abstract

The effects of pituitary adenylate cyclase activating polypeptide (PACAP)‐27 and PACAP‐38 were investigated and compared with vasoactive intestinal polypeptide (VIP) responses in voltage clamped preparations of rat jejunum. Under these conditions electrogenic ion secretion was continuously recorded. PACAP‐27 is the most potent secretagogue described thus far, exhibiting a concentration‐dependent dual secretory action. At low concentrations it stimulated rapid, transient secretory responses (not seen with either PACAP‐38 or VIP) and these were inhibited by tetrodotoxin (TTX). At higher nm concentrations of PACAP‐27 more prolonged secretory responses predominated which were insensitive to TTX. In the presence of TTX, the concentration‐response curve to PACAP‐27 gave an EC50 value of 29.4 ± 5.4 nm (n = 4) compared with 0.8 ± 0.1 nm (n = 9) for PACAP‐27 alone and 30.6 ± 5.6 nm (n = 5) for PACAP‐38. C‐terminal fragments of PACAP‐38 were not significantly effective. Blockade of muscarinic and nicotinic receptors partially inhibited the low concentration effects of PACAP‐27. Substance P densensitization and capsaicin pretreatment were effective at inhibiting the transient secretory PACAP‐27 responses. Evidence is presented for selective, high affinity PACAP‐27 receptors on submucous neurones innervating the mucosal region of the rat jejunum. 1992 British Pharmacological Society