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

We studied the effects of tachykinin receptor antagonists on fluid-induced, spontaneous net aboral propulsive complexes in isolated, vascularly perfused porcine ileal segments.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.NKI, NK2 or NK3 receptor antagonists (CP99994, SR48968 and SR 142801 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.We conclude that, in the porcine ileum, tachykinins mediate atropine-resistant net aboral propulsive complexes acting on NKI receptors.