Role of VIP1/PACAP receptors in postoperative ileus in rats

1 Vasoactive intestinal polypeptide (VIP) is an inhibitory neurotransmitter in the enteric nervous system. We investigated the role of VIP1/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 VIP1/PACAP receptor antagonist Ac-Hisl,D-Phe(2), K-15, R-16, VIP(3-7), GRF(8-27)-NH2 nor by the VIP1/PACAP receptor agonist K-15, R-16, VIP(I-7), GRF(8-27)-NH2 and the VIP2/PACAP receptor agonist RO 25-1553 (5 mu g kg(-1)). 4 However, the transit after laparotomy plus mechanical stimulation was significantly enhanced by the VIP1/PACAP receptor antagonist, whereas it was further inhibited by the VIP1/PACAP receptor agonist. The combination of the VIP1/PACAP receptor agonist and antagonist counteracted the effect of both drugs alone. The VIP2/PACAP receptor agonist did not after the effect of the VIP1/PACAP receptor antagonist. 5 The combination of the VIP1/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 VIP1/PACAP receptors, next to NO, in the pathogenesis of postoperative ileus. However, the combination of the VIP1/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.