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

Abstract

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.