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

Zsófia Lázár, Anaid Shahbazian, Rita Benkó, Gábor Tóth, Botond Penke, Loránd Barthó, Peter Holzer

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8 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)259-264
Number of pages6
JournalEuropean Journal of Pharmacology
Volume431
Issue number2
DOIs
Publication statusPublished - Nov 16 2001

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Keywords

  • (Guinea-pig)
  • Circular muscle contraction
  • PACAP (pituitary adenylate cyclase-activating peptide)
  • Peristaltic reflex
  • Small intestine
  • VIP receptor antagonist

ASJC Scopus subject areas

  • Pharmacology

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