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 vitro pharmacological actions of human alpha- and beta-CGRP applied as single concentrations to prostaglandin F2alpha precontracted segments of guinea pig basilar artery. To support the suggestion of a possible link between the pharmacological actions of alpha- and beta-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 alpha- or beta-CGRP. In another set of experiments, the time course of alpha- and beta-CGRP induced vasodilatation was investigated and concentration dependent responses of the two peptides were demonstrated. No significant differences between the actions of alpha- and 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 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 alpha- and beta-CGRP might be mediated via CRLR derived CGRP receptors.
Sams
A
A
Department of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen O. ansa@mail.dfh.dk
Yenidunya
A
A
Engberg
J
J
Jansen-Olesen
I
I
D000818:Animals; D001483:Base Sequence; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D058286:Calcitonin Receptor-Like Protein; D000242:Cyclic AMP / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015237:Dinoprost / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018003:Receptors, Calcitonin / Q000235:genetics / Q000502:physiology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000235:genetics / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
C545578:CALCRL protein, human; C108477:CRCP protein, human; D058286:Calcitonin Receptor-Like Protein; C545580:Calcrl protein, rat; C491562:Crcp protein, rat; D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D018003:Receptors, Calcitonin; D018015:Receptors, Calcitonin Gene-Related Peptide; D015237:Dinoprost; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide