Characterization of the CGRP receptor and mechanisms of action in rat mesenteric small arteries.
Rat alpha-calcitonin gene-related peptide-induced concentration-dependent (100 pM-10 nM) relaxations in rat mesenteric small arteries (i.d. approximately 220 microns) contracted with noradrenaline, prostaglandin F2 alpha or K+, however, the maximal relaxation depended on the precontractile stimulus, being highest (95%) in arteries contracted with PGF2 alpha and lowest (51%) in arteries contracted with 125 mM K+. The relaxation was inhibited between 10 pM and 1 nM by removal of the endothelium, but was not antagonized by glibenclamide (1 microM), tetraethylammonium (30 mM), apamine (0.3 microM) and 4-aminopyridine (3 mM). The concentration-response curve to rat alpha-CGRP and human beta-CGRP was shifted to the right in the presence of 1 microM human alpha-CGRP(8-37) indicating a receptor affinity, -log(KB[M]), equal to 7.2 and 7.0, respectively. It is concluded that the relaxation induced by CGRP depends minimally on the endothelium and K(+)-channel opening is not a principal process in the relaxing effect of CGRP, thus a third mechanism must mediate the relaxation in these vessels. The main CGRP receptor type mediating relaxation in rat mesenteric small arteries belongs to the CGRP1 subtype.
Lei
S
S
Department of Pharmacology, Aarhus University, Denmark.
Mulvany
M J
MJ
Nyborg
N C
NC
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
D015221:Potassium Channels; D018015:Receptors, Calcitonin Gene-Related Peptide; D015237:Dinoprost; D015740:Calcitonin Gene-Related Peptide