Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

Lázár, Z; Shahbazian, A; Benkó, R; Tóth, G; Penke, B; Barthó, L; Holzer, P.
PACAP-(6-38) inhibits the effects of vasoactive intestinal polypeptide, but not PACAP, on the small intestinal circular muscle.
EUR J PHARMACOL. 2001; 431: 259-264. Doi: 10.1016%2FS0014-2999%2801%2901451-0
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Co-Autor*innen der Med Uni Graz: Holzer Peter
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Abstract:: 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 microM) 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 microM) and indomethacin (3 microM), spontaneous myogenic activity was inhibited by VIP (5-30 nM). This effect was significantly reduced by a pretreatment with PACAP-(6-38) (3 microM). 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.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Gastrointestinal Motility - drug effects; Guinea Pigs - drug effects; Ileum - drug effects; In Vitro - drug effects; Intestine, Small - drug effects; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Neuropeptides - pharmacology; Peptide Fragments - pharmacology; Peristalsis - pharmacology; Pituitary Adenylate Cyclase-Activating Polypeptide - pharmacology; Pressure - pharmacology; Research Support, Non-U.S. Gov't - pharmacology; Vasoactive Intestinal Peptide - antagonists and inhibitors
Find related publications in this database (Keywords): peristaltic reflex; circular muscle contraction; small intestine; (guinea-pig); VIP receptor antagonist; PACAP (pituitary adenylate cyclase-activating; peptide)