Pharmacological characterization of CGRP1 receptor subtype in the vascular system of the rat: studies with hCGRP fragments and analogs.
In order to examine whether the truncated fragments of hCGRP, hCGRP(8-37) or hCGRP(12-37), behave as competitive CGRP receptor antagonists in the vascular system of the rat, systemic blood pressure was continually monitored in pentobarbital-anesthetized Sprague-Dawley rats. The IV administration of 7.9-527 pmol hCGRP/rat caused dose-related reductions in mean arterial blood pressure that lasted, depending on the dose, about 3-10 min. In contrast, hCGRP fragments 8-37 or 12-37 proved inactive up to 60,000 pmol/rat. Pretreatment with either 10 or 30 nmol hCGRP(8-37) or 20 or 90 nmol hCGRP(12-37)/rat reduced the magnitude of the CGRP-induced hypotensive responses caused by 79 pmol hCGRP/rat; pretreatment with 10 nmol of the hCGRP fragments displaced about 3-fold the hCGRP as well as the [Cys(ACM)2.7]hCGRP dose-response curve to the right in a parallel fashion. The specificity of hCGRP(8-37) as a CGRP receptor antagonist was documented by the finding that it did not antagonize the hypotensive responses induced with bradykinin, histamine or substance P.
Donoso
M V
MV
Department of Physiology, Faculty of Biological Sciences, P. Catholic University of Chile, Santiago.
Fournier
A
A
St-Pierre
S
S
Huidobro-Toro
J P
JP
D000818:Animals; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000145:classification* / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology
D010446:Peptide Fragments; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; C058636:calcitonin gene-related peptide (8-37); D013373:Substance P; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide; D001920:Bradykinin