Pharmacological characterization of VIP and PACAP receptors in the human meningeal and coronary artery
Pharmacological characterization of VIP and PACAP receptors in the human meningeal and coronary artery
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DOI：
10.1177/0333102410375624
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发表时间：
2011-01-01
期刊：
影响因子：
4.9
通讯作者：
Gupta, Saurabh
中科院分区：
文献类型：
--
作者：
Chan, Kayi Y.;Baun, Michael;Gupta, Saurabh
目的：对垂体腺苷酸环化酶激活多肽（PACAPs）、血管活性肠肽（VIP）以及人脑膜（在偏头痛中起作用）和冠状动脉（潜在副作用）中的VPAC(1)、VPAC(2)和PAC(1)受体进行药理学表征。方法：构建PACAP38、PACAP27、VIP及VPAC(1)受体激动剂（[Lys15, Arg16, Leu27]-VIP[1-7]-GRF[8-27]）在PAC(1)受体拮抗剂PACAP6-38或VPAC1受体拮抗剂PG97269缺失或存在情况下的浓度响应曲线。采用qPCR检测mRNA表达量。结果：PACAP38在两条动脉中的作用均低于VIP。两种多肽在脑膜中的效价和疗效均低于冠状动脉，而VPAC(1)受体mRNA在脑膜动脉中的表达更为明显。PACAP6-38降低了PACAP27的E-max，而PG97269仅在冠状动脉右移vip诱导的舒张曲线。结论：VIP和PACAP的直接血管扩张作用可能不如其在偏头痛发病中的中心作用重要。
Objective: We pharmacologically characterized pituitary adenylate cyclase-activating polypeptides (PACAPs), vasoactive intestinal peptide (VIP) and the VPAC(1), VPAC(2) and PAC(1) receptors in human meningeal (for their role in migraine) and coronary (for potential side effects) arteries.Methods: Concentration response curves to PACAP38, PACAP27, VIP and the VPAC(1) receptor agonist ([Lys15, Arg16, Leu27]-VIP[1-7]-GRF[8-27]) were constructed in the absence or presence of the PAC(1) receptor antagonist PACAP6-38 or the VPAC1 receptor antagonist, PG97269. mRNA expression was measured using qPCR.Results: PACAP38 was less potent than VIP in both arteries. Both peptides had lower potency and efficacy in meningeal than in coronary arteries, while mRNA expression of VPAC(1) receptor was more pronounced in meningeal arteries. PACAP6-38 reduced the E-max of PACAP27, while PG97269 right-shifted the VIP-induced relaxation curve only in the coronary arteries.Conclusion: The direct vasodilatory effect of VIP and PACAP might be less relevant than the central effect of this compound in migraine pathogenesis.