Jansen-Olesen I, Mortensen A, Edvinsson L
Department of Experimental Vascular Research, Glostrup Hospital, University of Copenhagen, Denmark.
Cephalalgia. 1996 Aug;16(5):310-6. doi: 10.1046/j.1468-2982.1996.1605310.x.
The vasomotor effects of calcitonin gene-related peptide (CGRP) analogues have been studied in circular segments of fresh human cerebral arteries obtained at neurosurgical operations using a sensitive in vitro system. Human alpha-CGRP, human beta-CGRP, rat alpha-CGRP and rat beta-CGRP induced strong and potent relaxation of precontracted circular vessel segments. The Imax (maximum relaxant effect) to human calcitonin was low and the pD2 (concentration for half maximum effect) 7.7 was much lower than that of CGRP. The CGRP-1, antagonist human alpha-CGRP8-37 blocked the response to human alpha-CGRP but not to human beta-CGRP, while the putative antagonist [Tyr]CGRP28-37 did not. Capsaicin (10(-15)-10(-8)M) caused relaxation of the cerebral arteries by 22% of precontraction. Pre-treatment with 10(-6)M human alpha-CGRP8-37 inhibited this relaxation. Human alpha-CGRP increased the cyclic AMP content of human cerebral arteries in a concentration-dependent manner. This increase in adenylyl cyclase activity was blocked by human alpha-CGRP8-37. The results suggest that CGRP-1 receptors coupled to adenylyl cyclase are present in human cerebral arteries.
利用一种灵敏的体外系统，在神经外科手术中获取的新鲜人脑动脉环段中研究了降钙素基因相关肽（CGRP）类似物的血管运动效应。人α-CGRP、人β-CGRP、大鼠α-CGRP和大鼠β-CGRP均可引起预收缩的血管环段强烈而有效的舒张。人降钙素的Imax（最大舒张效应）较低，pD2（半数最大效应浓度）为7.7，远低于CGRP。CGRP-1拮抗剂人α-CGRP8-37可阻断对人α-CGRP的反应，但不阻断对人β-CGRP的反应，而假定的拮抗剂[Tyr]CGRP28-37则无此作用。辣椒素（10^(-15)-10^(-8)M）可使脑动脉舒张，幅度为预收缩的22%。用10^(-6)M人α-CGRP8-37预处理可抑制这种舒张。人α-CGRP可使人脑动脉的环磷酸腺苷含量呈浓度依赖性增加。腺苷酸环化酶活性的这种增加被人α-CGRP8-37阻断。结果表明，与人脑动脉中与腺苷酸环化酶偶联的CGRP-1受体存在。
