Pharmacological coupling and functional role for CGRP receptors in the vasodilation of rat pial arterioles.
In this study, we investigated the signal transduction underlying the vasodilator action of calcitonin gene-related peptide (CGRP) in the rat pial arterioles. In an in vivo experiment, changes in pial arterial diameters (20.2 +/- 1.9 microns) were observed under suffusion with mock cerebrospinal fluid containing CGRP (10(-9)-10(-7) M) directly through a closed cranial window. Changes in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in response to CGRP and levcromakalim were measured in the pial arterioles in an in vitro experiment. CGRP-induced vasodilation and cAMP production were significantly inhibited by specific CGRP antibody serum and CGRP-(8-37) fragment, suggesting involvement of the CGRP1 receptor subtype. Vasodilation and increase in cAMP production evoked by CGRP were inhibited not only by glibenclamide (ATP-sensitive K+ channel blocker) but also by charybdotoxin (large-conductance Ca(2+)-activated K+ channel blocker), but this was not the case for the isoproterenol-induced vasodilation and cAMP production. These findings implicate the ATP-sensitive K+ channels and the large-conductance Ca(2+)-activated K+ channels in the CGRP receptor-coupled cAMP production for vasodilation. Further study is required to identify whether the cAMP-dependent K+ channel activation is related to CGRP-induced vasorelaxation of the rat pial arterioles.
Hong
K W
KW
Department of Pharmacology, College of Medicine, Pusan National University, Korea.
Yoo
S E
SE
Yu
S S
SS
Lee
J Y
JY
Rhim
B Y
BY
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001578:Benzopyrans / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology / Q000494:pharmacology; D019806:Cromakalim; D000242:Cyclic AMP / Q000378:metabolism; D007106:Immune Sera / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D026902:Potassium Channel Blockers; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D001578:Benzopyrans; D007106:Immune Sera; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; D011758:Pyrroles; D018015:Receptors, Calcitonin Gene-Related Peptide; D019806:Cromakalim; C058636:calcitonin gene-related peptide (8-37); D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D007545:Isoproterenol