PACAP-(6-38) inhibits the effects of vasoactive intestinal polypeptide, but not PACAP, on the small intestinal circular muscle.
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.
Lázár
Z
Z
Department of Pharmacology and Pharmacotherapy, University of Pécs, Szigeti u. 12, H-7643 Pécs, Hungary. lorand.bartho@aok.pte.hu
Shahbazian
A
A
Benkó
R
R
Tóth
G
G
Penke
B
B
Barthó
L
L
Holzer
P
P
D000818:Animals; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010528:Peristalsis; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011312:Pressure; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D009479:Neuropeptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D014660:Vasoactive Intestinal Peptide