Neurokinin A-induced vasoconstriction and muscular contraction in the rat isolated stomach: mediation by distinct and unusual neurokinin2 receptors.
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 [betaAla8]-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.
Lippe
I
I
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Wachter
C H
CH
Holzer
P
P
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D015288:Neurokinin A / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
D018041:Receptors, Neurokinin-2; D015288:Neurokinin A