犬大脑中动脉中介导对P物质舒张反应的受体的特性：无证据表明P物质参与神经源性介导的舒张反应。

Characterization of the receptor mediating relaxation to substance P in canine middle cerebral artery: no evidence for involvement of substance P in neurogenically mediated relaxation.

作者信息

Stubbs C M, Waldron G J, Connor H E, Feniuk W

机构信息

Department of Neuropharmacology, Glaxo Group Research, Ware, Herts.

出版信息

Br J Pharmacol. 1992 Apr;105(4):875-80. doi: 10.1111/j.1476-5381.1992.tb09071.x.

DOI:10.1111/j.1476-5381.1992.tb09071.x

PMID:1380374

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908684/

Abstract

The aim of this study was to characterize the neurokinin receptor which mediates relaxation of dog isolated middle cerebral artery by the use of selective agonists and antagonists and to establish whether substance P is involved in the neurogenically mediated relaxant response in this vessel. 2. Substance P caused concentration-related, endothelium-dependent relaxations of dog isolated middle cerebral artery, contracted with prostaglandin F2 alpha. The selective NK1 receptor agonists, GR73632 and substance P methyl ester (SPOMe), also caused relaxation with similar maximum effects to those of substance P. GR73632 and SPOMe were approximately 20 times and 6 times less potent respectively than substance P. The selective NK2 and NK3 receptor agonists, GR64349 and senktide, were only weakly active in causing relaxation being at least 425 times and 245 times less potent respectively than substance P. 3. The selective NK1 receptor antagonist, GR82334, was a potent, specific, competitive antagonist of the relaxant effects of substance P. In contrast, the selective NK2 receptor antagonist, R396 (10 microM) had no effect on the response to substance P. 4. Electrical field stimulation of dog isolated middle cerebral artery, contracted with prostaglandin F2 alpha, caused neurogenically mediated, non-adrenergic non-cholinergic (NANC) relaxations. These NANC relaxations were unaffected by endothelium removal, GR82334 (10 microM) or by capsaicin (10 microM) treatment. However, the nitric oxide synthesis inhibitor, L-NG-monomethyl arginine methyl ester (L-NMMA) (100 microM) markedly attenuated the response to electrical stimulation. 5. These results suggest that substance P causes relaxation of dog isolated middle cerebral artery via activation of NK1 receptors. However, substance P does not appear to be involved in NANC neurotransmission. In contrast, the marked inhibitory effect of L-NMMA on NANC relaxations implicates nitric oxide in NANC neurotransmission in this vessel.

摘要

本研究的目的是利用选择性激动剂和拮抗剂来鉴定介导犬离体大脑中动脉舒张的神经激肽受体，并确定P物质是否参与该血管的神经源性介导的舒张反应。2. P物质引起犬离体大脑中动脉与前列腺素F2α预收缩后的浓度依赖性、内皮依赖性舒张。选择性NK1受体激动剂GR73632和P物质甲酯（SPOMe）也引起舒张，其最大效应与P物质相似。GR73632和SPOMe的效价分别比P物质低约20倍和6倍。选择性NK2和NK3受体激动剂GR64349和senktide在引起舒张方面活性较弱，效价分别比P物质低至少425倍和245倍。3. 选择性NK1受体拮抗剂GR82334是P物质舒张作用的强效、特异性竞争性拮抗剂。相比之下，选择性NK2受体拮抗剂R396（10μM）对P物质的反应无影响。4. 对与前列腺素F2α预收缩的犬离体大脑中动脉进行电场刺激，可引起神经源性介导的非肾上腺素能非胆碱能（NANC）舒张。这些NANC舒张不受内皮去除、GR82334（10μM）或辣椒素（10μM）处理的影响。然而，一氧化氮合成抑制剂L-NG-单甲基精氨酸甲酯（L-NMMA）（100μM）显著减弱了对电场刺激的反应。5. 这些结果表明，P物质通过激活NK1受体引起犬离体大脑中动脉舒张。然而，P物质似乎不参与NANC神经传递。相反，L-NMMA对NANC舒张的显著抑制作用表明一氧化氮参与了该血管的NANC神经传递。