PACAP-(6–38) inhibits the effects of vasoactive intestinal polypeptide, but not PACAP, on the small intestinal circular muscle

• Published in: European journal of pharmacology 2001-11, Vol.431 (2), p.259-264
• Main Authors: Lázár, Zsófia, Shahbazian, Anaid, Benkó, Rita, Tóth, Gábor, Penke, Botond, Barthó, Loránd, Holzer, Peter
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Circular muscle contraction; Fundamental and applied biological sciences. Psychology; Gastrointestinal Motility - drug effects; Guinea Pigs; Guinea-pig; Ileum - drug effects; In Vitro Techniques; Intestine, Small - drug effects; Intestine. Mesentery; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Neuropeptides - pharmacology; PACAP (pituitary adenylate cyclase-activating peptide); Peptide Fragments - pharmacology; Peristalsis; Peristaltic reflex; Pituitary Adenylate Cyclase-Activating Polypeptide; Pressure; Small intestine; Vasoactive Intestinal Peptide - antagonists & inhibitors; Vasoactive Intestinal Peptide - pharmacology; Vertebrates: digestive system; VIP receptor antagonist
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)01451-0

Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide-(1–38) (PACAP) have been found to stimulate distension-induced peristaltic motility in the guinea-pig isolated small intestine. In this study, we tested whether the putative VIP/PACAP receptor antagonist PACAP-(6–38) counteracts the properistaltic effect of VIP and PACAP in isolated segments of the guinea-pig small intestine. VIP (100 nM) and PACAP (30 nM) had a stimulatory effect, i.e., lowered the peristaltic pressure threshold at which peristaltic waves were triggered and enhanced the frequency of peristaltic waves. PACAP-(6–38) (3 μM) was per se without effect on peristalsis but prevented or reversed the peristaltic motor stimulation caused by VIP, when it was given before or after the agonist, respectively. PACAP-(6–38), however, failed to antagonize the properistaltic effect of PACAP. In ileal circular strips treated with tetrodotoxin (1 μM) and indomethacin (3 μM), spontaneous myogenic activity was inhibited by VIP (5–30 nM). This effect was significantly reduced by a pretreatment with PACAP-(6–38) (3 μM). A similar inhibition by PACAP-(1–38) (10–500 nM) was not influenced by the antagonist. It is concluded that PACAP-(6–38) is a VIP receptor antagonist, both in the peristaltic motor pathways and at the level of the circular muscle of the guinea-pig small intestine. The lack of a motor effect of PACAP-(6–38) on its own indicates that VIP acting on PACAP-(6–38)-sensitive receptors (located on neurons and/or the smooth muscle) is unlikely to participate in peristaltic motor regulation.