Equipotent in vitro actions of alpha- and beta-CGRP on guinea pig basilar artery are likely to be mediated via CRLR derived CGRP receptors

The aim of the present study was to investigate and compare specific in vit ro pharmacological actions of human alpha- and beta-CGRP applied as single concentrations to prostaglindin F-2 alpha precontracted segments of guinea pig basilar artery. To support the suggestion of a possible link between th e pharmacological actions of alpha- and beta-CGRP and a specific receptor, we wished to determine whether mRNAs required for the expression of calcito nin receptor-like receptor (CRLR) derived CGRP receptors were present in th e guinea pig basilar artery. In the pharmacological experiments we demonstr ated an increase in the cAMP content by 2.5-fold and a concomitant signific ant vasorelaxation of the precontracted basilar artery segments following 1 min of stimulation by 10(-7) M alpha- or beta-CGRP. In another set of expe riments, the time course of alpha- and beta-CGRP induced vasodilatation was investigated and concentration dependent responses of the two peptides wer e demonstrated. No significant differences between the actions of alpha- an d beta-CGRP regarding induction of cAMP formation, amount of vasodilatation , time course of vasodilatation and mode of inhibition by the CGRP receptor antagonist, human alpha-CGRP(8-37), could be detected. The presence of mRN A encoding the guinea pig CRLR and the guinea pig CGRP receptor component p rotein (RCP) in the guinea pig basilar artery was demonstrated by RT-PCR me thods. Furthermore, a partial sequence of mRNA encoding the guinea pig CRLR was determined. The expression in this tissue of a CRLR derived CGRP recep tor and a functional RCP is therefore likely, and the equipotent pharmacolo gical actions of alpha- and beta-CGRP might be mediated via CRLR derived CG RP receptors. (C) 1999 Elsevier Science B.V. All rights reserved.