Role of VIP₁/PACAP receptors in postoperative ileus in rats

Abstract

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-Phe², K¹⁵, R¹⁶, VIP(3–7), GRF(8–27)-NH₂ nor by the VIP₁/PACAP receptor agonist K¹⁵, R¹⁶, VIP(1–7), GRF(8–27)-NH₂ and the VIP₂/PACAP receptor agonist RO 25-1553 (5 μg 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 alter 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.

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