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

Add time:08/25/2019    Source:sciencedirect.com

The aim of the present study was to investigate and compare specific in vitro pharmacological actions of human α- and β-CGRP applied as single concentrations to prostaglandin F2α precontracted segments of guinea pig basilar artery. To support the suggestion of a possible link between the pharmacological actions of α- and β-CGRP and a specific receptor, we wished to determine whether mRNAs required for the expression of calcitonin receptor-like receptor (CRLR) derived CGRP receptors were present in the guinea pig basilar artery. In the pharmacological experiments we demonstrated an increase in the cAMP content by 2.5-fold and a concomitant significant vasorelaxation of the precontracted basilar artery segments following 1 min of stimulation by 10−7 M α- or β-CGRP. In another set of experiments, the time course of α- and β-CGRP induced vasodilatation was investigated and concentration dependent responses of the two peptides were demonstrated. No significant differences between the actions of α- and β-CGRP regarding induction of cAMP formation, amount of vasodilatation, time course of vasodilatation and mode of inhibition by the CGRP receptor antagonist, human α-CGRP8–37, could be detected. The presence of mRNA encoding the guinea pig CRLR and the guinea pig CGRP receptor component protein (RCP) in the guinea pig basilar artery was demonstrated by RT-PCR methods. Furthermore, a partial sequence of mRNA encoding the guinea pig CRLR was determined. The expression in this tissue of a CRLR derived CGRP receptor and a functional RCP is therefore likely, and the equipotent pharmacological actions of α- and β-CGRP might be mediated via CRLR derived CGRP receptors.

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