Lam F F
Department of Pharmacology, The Chinese University of Hong Kong, Shatin, New Territories, SAR, China.
J Cardiovasc Pharmacol. 2000 Apr;35(4):646-52. doi: 10.1097/00005344-200004000-00019.
The receptor types mediating sensory neuropeptide-induced coronary vasodilatation were elucidated on isolated guinea pig hearts perfused with isotonic buffer containing 20 mM KCl. Substance P and the selective neurokinin-1 (NK1) receptor agonist [Sar9, Met(O2)11]-substance P produced dose-dependent reductions in perfusion pressure, but the selective NK2 receptor agonist [Nle10]-neurokinin A4-10 and the selective NK3 receptor agonist [MePhe7]-neurokinin B produced no change. The vasorelaxant effects of substance P and the NK1 receptor agonist were abolished by the selective NK1 receptor antagonist FK888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L-prolyl]-N-methy l-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide), whereas the selective NK2 receptor antagonist SR48968 ((S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl )-butyl] benzamide) and the selective NK3 receptor antagonist SR142801 ((S)-(N)-( 1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)4-p henylpiperidin-4-yl)-N-methylacetamide) produced partial inhibition on their responses. Calcitonin gene-related peptide (CGRP) produced dose-dependent vasodilatation on the guinea pig coronary blood vessels, which was significantly (p = 0.0067) inhibited by the selective CGRP1 receptor antagonist hCGRP8-37. The selective CGRP2 receptor agonist [Cys(acetomethoxy)2,7]CGRP had no effect on perfusion pressure. These results demonstrate that the sensory neuropeptides substance P and CGRP are effective vasodilators of the guinea pig coronary vascular bed. The receptor types mediating their vasorelaxant effects were identified to be the NK1 receptors and CGRP1 receptors, respectively.
在灌注含20 mM KCl等渗缓冲液的离体豚鼠心脏上，阐明了介导感觉神经肽诱导冠状动脉舒张的受体类型。P物质和选择性神经激肽-1（NK1）受体激动剂[Sar9, Met(O2)11]-P物质可使灌注压呈剂量依赖性降低，但选择性NK2受体激动剂[Nle10]-神经激肽A4-10和选择性NK3受体激动剂[MePhe7]-神经激肽B则无变化。P物质和NK1受体激动剂的血管舒张作用被选择性NK1受体拮抗剂FK888（N2-[(4R)-4-羟基-1-(1-甲基-1H-吲哚-3-基)羰基-L-脯氨酰]-N-甲基-N-苯基甲基-3-(2-萘基)-L-丙氨酰胺）消除，而选择性NK2受体拮抗剂SR48968（(S)-N-甲基-N-[4-乙酰氨基-4-苯基哌啶基)-2-(3,4-二氯苯基)-丁基]苯甲酰胺）和选择性NK3受体拮抗剂SR142801（(S)-(N)-(1-(3-(1-苯甲酰基-3-(3,4-二氯苯基)哌啶-3-基)丙基)4-苯基哌啶-4-基)-N-甲基乙酰胺）对其反应产生部分抑制。降钙素基因相关肽（CGRP）对豚鼠冠状动脉血管产生剂量依赖性舒张作用，该作用被选择性CGRP1受体拮抗剂hCGRP8-37显著（p = 0.0067）抑制。选择性CGRP2受体激动剂[Cys(乙酰甲氧基)2,7]CGRP对灌注压无影响。这些结果表明，感觉神经肽P物质和CGRP是豚鼠冠状动脉血管床有效的血管舒张剂。介导其血管舒张作用的受体类型分别被确定为NK1受体和CGRP1受体。
