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

Authors


Inger Jansen-Olesen, Department, of Experimental Vascular Research, Elevbolighuset 4 sal Glostrup Hospital, University of Copenhagen, DK-2600 Glostrup, Denmark. Tel. +45 4396 4333, fax. +45 4342 3570.

Abstract

The vasomotor effects of calcilonin gene-related peptide (CGRP) analogues have been studied in circular segments of fresh human cereoral arteries obtained at neurosurgical operations using a sensitive in vitro system. Human a-CGRP, human b-CGRP, rat a-CGRP and rat b-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 a-CGRP8–37 blocked the response to human a-CGRP but not to human b-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 precontract on. Pre-treatment with 10−6 M human a-CGRP8–37 inhibited this relaxation. Human a-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 a-CGRP8–37. The results suggest that CGRP-1 receptors coupled to adenylyl cyclase are present in human cerebral arteries.

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