Tachykinin NK1 Receptors Mediate Atropine-Resistant Net Aboral Propulsive Complexes in Porcine Ileum

Abstract

Background: We studied the effects of tachykinin receptor antagonists on fluid-induced, spontaneous net aboral propulsive complexes in isolated, vascularly perfused porcine ileal segments. Methods: Fluid was instilled at a constant rate into the proximal opening of the segment, resulting in regular, rapidly propagating propulsive complexes along the entire ileal segment in the aboral direction. Results: NK1, NK2 or NK3 receptor antagonists (CP99994, SR48968 and SR142801 all at 10 -6 M) had no effect on the frequency of propulsive complexes. Atropine (10 -6 M) abolished the propulsive complexes for 15.0 ± 1.3 min ( n = 18). In spite of continued atropine infusion, the propulsive complexes reappeared. Infusion of the NK1 receptor antagonist CP99994 (10 -6 M) during continued atropine infusion blocked net aboral propulsive complexes in 5 experiments for 12.2 ± 2.4 min and resulted in motor paralysis in 2 experiments. SP release, measured in the venous effluent, was significantly increased in relation to propulsive complexes during atropine infusion. Conclusion: We conclude that, in the porcine ileum, tachykinins mediate atropine-resistant net aboral propulsive complexes acting on NK1 receptors.