P物质诱导犬脑动脉内皮依赖性收缩：NK1受体和血栓素A2的参与

Endothelium-dependent contraction induced by substance P in canine cerebral arteries: involvement of NK1 receptors and thromboxane A2.

作者信息

Shirahase H, Murase K, Kanda M, Kurahashi K, Nakamura S

机构信息

Pharmacology Division, Radioisotope Research Center, Kyoto University, Japan.

出版信息

Life Sci. 1999;64(3):211-9. doi: 10.1016/s0024-3205(98)00553-0.

DOI:10.1016/s0024-3205(98)00553-0

PMID:10027752

Abstract

We characterized the endothelial responses to substance P (SP) in the isolated canine cerebral artery. SP caused concentration-dependent contraction at 10(-10) - 10(-7) M and relaxation at 10(-10) and 10(-9) M, which were abolished by removal of the endothelium. The SP-induced endothelium-dependent relaxation (EDR) was suppressed, while the endothelium-dependent contraction (EDC) was increased by repeated application. The EDC induced by SP (10(-7) M) was attenuated by SR-140333 (10(-9) - 10(-7) M) and CP-99994 (10(-7) M), both NK1 antagonists, but not by SR-48968 (10(-7) M), an NK2 antagonist, or four antagonistic SP analogues (10(-6) M). The EDC induced by SP (10(-7) M) was attenuated by aspirin (10(-5) M), a cyclooxygenase inhibitor, OKY-046 (10(-5) M), a TXA2 synthetase inhibitor and ONO-3708 (10(-8) M), a TXA2 antagonist. Neurokinin A (10(-7) M) but not neurokinin B (10(-7) M) caused EDC similar to that induced by SP. In conclusion, SP induces EDC via endothelial NK1 receptors and TXA2 production in canine cerebral arteries.

摘要

我们对离体犬脑动脉中内皮细胞对P物质（SP）的反应进行了表征。SP在10^(-10) - 10^(-7) M浓度范围内引起浓度依赖性收缩，在10^(-10)和10^(-9) M时引起舒张，去除内皮后这些反应消失。重复应用时，SP诱导的内皮依赖性舒张（EDR）受到抑制，而内皮依赖性收缩（EDC）增强。SP（10^(-7) M）诱导的EDC被两种NK1拮抗剂SR - 140333（10^(-9) - 10^(-7) M）和CP - 99994（10^(-7) M）减弱，但不被NK2拮抗剂SR - 48968（10^(-7) M）或四种拮抗SP类似物（10^(-6) M）减弱。SP（10^(-7) M）诱导的EDC被环氧化酶抑制剂阿司匹林（10^(-5) M）、TXA2合成酶抑制剂OKY - 046（10^(-5) M）和TXA2拮抗剂ONO - 3708（10^(-8) M）减弱。神经激肽A（10^(-7) M）而非神经激肽B（10^(-7) M）引起类似于SP诱导的EDC。总之，在犬脑动脉中，SP通过内皮NK1受体和TXA2生成诱导EDC。