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Role of VIP 1 /PACAP receptors in postoperative ileus in rats
Author(s) -
De Winter Benedicte Y.,
Robberecht Patrick,
Boeckxstaens Guy E.,
De Man Joris G.,
Moreels Tom G.,
Herman Arnold G.,
Pelckmans Paul A.
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701954
Subject(s) - receptor , endocrinology , medicine , neuroscience , anesthesia , biology
1 Vasoactive intestinal polypeptide (VIP) is an inhibitory neurotransmitter in the enteric nervous system. We investigated the role of VIP 1 /PACAP receptors in postoperative ileus in rats. 2 Different degrees of inhibition of the gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy or laparotomy plus mechanical stimulation of the gut. 3 The transit after skin incision or laparotomy was not altered by the VIP 1 /PACAP receptor antagonist Ac‐Hisl,D‐Phe 2 , K 15 , R 16 , VIP(3–7), GRF(8–27)‐NH 2 nor by the VIP 1 /PACAP receptor agonist K 15 , R 16 , VIP(1–7), GRF(8–27)‐NH 2 and the VIP 2 /PACAP receptor agonist RO 25‐1553 (5 μg kg −1 ). 4 However, the transit after laparotomy plus mechanical stimulation was significantly enhanced by the VIP 1 /PACAP receptor antagonist, whereas it was further inhibited by the VIP 1 /PACAP receptor agonist. The combination of the VIP 1 /PACAP receptor agonist and antagonist counteracted the effect of both drugs alone. The VIP 2 /PACAP receptor agonist did not alter the effect of the VIP 1 /PACAP receptor antagonist. 5 The combination of the VIP 1 /PACAP receptor antagonist plus the nitric oxide (NO) synthase inhibitor l ‐nitroarginine had no effect on the transit after laparotomy plus mechanical stimulation, while the transit after skin incision was significantly decreased. 6 These findings suggest the involvement of VIP 1 /PACAP receptors, next to NO, in the pathogenesis of postoperative ileus. However, the combination of the VIP 1 /PACAP antagonist and the NO synthase inhibitor abolished the beneficial effect of each drug alone, suggesting the need for one of the inhibitory neurotransmitters to enable normal gastrointestinal transit.British Journal of Pharmacology (1998) 124 , 1181–1186; doi: 10.1038/sj.bjp.0701954