Pharmacological coupling and functional role for the cgrp receptors
in the vasodilation of rat pial arterioles.
Hong, Ki Whan, Sung-Eun Yoo, Sung Suk Yu, Jung Yoon Lee, and Byung
Yong Rhim.
Department of Pharmacology, College of Medicine, Pusan National
University, Pusan 602-739; Center for Biofunctional Molecules, Pohang
and Korea Research Institute of Chemical Technology, Dajeon,
Korea
APStracts 2:0289H, 1995.
In this study, we investigated the signal transduction underlying the
vasodilator action of calcitonin gene-related peptide (CGRP) in the
rat pial arterioles. As an in vivo experiment, changes in pial
arterial diameters (mean 20.2 [acute]i 1.9 um) were observed under
suffusion with mock CSF containing CGRP (10-9 10-7 M) directly
through a closed cranial window. Otherwise, changes in intracellular
cAMP accumulation in response to CGRP and levcromakalim were measured
in the pial arterioles in the in vitro experiment. Both CGRP-induced
vasodilation and cAMP production were significantly inhibited by
specific CGRP antibody serum and CGRP (8-37) fragment, suggesting
involvement of CGRP1 receptor subtype. Both 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 Ca2+-activated K+ channel blocker),
but it was not the same case for the isoproterenol-induced
vasodilation and cAMP production. These findings indicate an
implication of the ATP-sensitive K+ channels and the large
conductance Ca2+-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
with CGRP-induced vasorelaxation of the rat pial arterioles.
Received 24 January 1995; accepted in final form 13 June 1995.
APS Manuscript Number H63-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.