Calcitonin gene-related peptide is released from capsaicin-sensitive nerve fibres and induces vasodilatation of human cerebral arteries concomitant with activation of adenylyl cyclase

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 patent relaxation of precontracted circular vessel segments. The I-max (maximum relaxant effect) to human calcitonin was low and the pD(2) (concentration for half maximum effect) 7.7 was much lower than that of CGRP. The CGRP-1, antagonist human alpha-CGRP(8-37) blocked the response to human alpha-CGRP but not to human beta-CGRP, while the putative antagonist [Tyr]CGRP(28-37) 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-CGRP(8-37) 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-CGRP(8-37). The results suggest that CGRP-1 receptors coupled to adenylyl cyclase are present in human cerebral arteries.