Vol. 281, Issue 3, 1294-1302, 1997

Neurokinin A-Induced Vasoconstriction and Muscular Contraction in the Rat Isolated Stomach: Mediation by Distinct and Unusual Neurokinin₂ Receptors¹

Irmgard Th. Lippe, Christof H. Wachter and Peter Holzer

Department of Experimental and Clinical Pharmacology, University of Graz, Universitätsplatz 4, A-8010 Graz, Austria

This study examined the pharmacological identity of the tachykinin receptors which in the rat stomach mediate vasoconstriction and muscular contraction. The vasculature of the rat isolated stomach was perfused with oxygenated Krebs buffer containing 3% dextran. Vasoconstrictor responses were recorded as increases in the vascular perfusion pressure and gastric contractions were measured as increases in the intraluminal pressure. By examining the effects of selective agonists and antagonists for tachykinin neurokinin (NK)₁, NK₂ and NK₃ receptors it was found that the vasculature contained only NK₂ receptors that were activated by the NK₂ receptor agonist [Ala⁸]-NKA-(4-10) and inhibited by the NK₂ receptor antagonists MEN-10,627 and GR-94,800. However, the vasoconstrictor action of NKA was blocked only when the preparations were exposed to a combination of NK₁, NK₂ and NK₃ receptor antagonists (SR-140,333, MEN-10,627, PD-161,182). In contrast, the NKA-evoked contraction of the gastric musculature was suppressed by NK₂ receptor antagonists but little affected by NK₁ or NK₃ receptor antagonists. This observation was consistent with the predominance of NK₂ receptors on the muscle as revealed by the effects of receptor-selective NK₁, NK₂ and NK₃ agonists and antagonists. These results demonstrate that the major tachykinin receptor type present on the gastric vasculature and musculature is a NK₂ receptor that is sensitive to receptor-selective agonists and antagonists. The NKA-evoked gastric contraction is also primarily due to NK₂ receptor activation, whereas the NKA-induced vasoconstriction is mediated by a distinct and unusual type of NK₂-like receptor that is blocked by a combination of NK₁, NK₂ and NK₃ receptor antagonists only.