Lippe I, Wachter C H, Holzer P
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
J Pharmacol Exp Ther. 1997 Jun;281(3):1294-302.
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.
本研究检测了速激肽受体的药理学特性，这些受体在大鼠胃中介导血管收缩和肌肉收缩。将分离的大鼠胃血管用含3%葡聚糖的氧合 Krebs 缓冲液进行灌注。血管收缩反应记录为血管灌注压的升高，胃收缩则通过管腔内压的升高来测量。通过检测速激肽神经激肽（NK）1、NK2和NK3受体的选择性激动剂和拮抗剂的作用，发现血管系统仅含有NK2受体，这些受体可被NK2受体激动剂[β丙氨酸8]-NKA-(4 - 10)激活，并被NK2受体拮抗剂MEN - 10,627和GR - 94,800抑制。然而，只有当制剂暴露于NK1、NK2和NK3受体拮抗剂（SR - 140,333、MEN - 10,627、PD - 161,182）的组合时，NKA的血管收缩作用才被阻断。相反，NKA引起的胃肌肉收缩可被NK2受体拮抗剂抑制，但受NK1或NK3受体拮抗剂的影响很小。这一观察结果与受体选择性NK1、NK2和NK3激动剂及拮抗剂的作用所揭示的肌肉上NK2受体占优势相一致。这些结果表明，胃血管系统和肌肉组织上存在的主要速激肽受体类型是对受体选择性激动剂和拮抗剂敏感的NK2受体。NKA引起的胃收缩也主要是由于NK2受体激活，而NKA诱导的血管收缩是由一种独特且不寻常的NK2样受体介导的，该受体仅被NK1、NK2和NK3受体拮抗剂的组合所阻断。
