Potassium channels mediate vasodilatory response to calcitonin-gene-related peptide in rat tail artery

We investigated the relaxant effects of exogenous calcitonin-gene-related peptide (CGRP) in isolated tail arteries from rats. CGRP caused a dose-dependent relaxation of tail artery strips precontracted with 3 x 10^-7 M norepinephrine (ED₅₀ = 2.2 nM; max = 70% ± 5%, n = 4). Indomethacin (5 μM) and removal of the endothelium had little effect on CGRP-induced relaxation. Tetraethylammonium (TEA) (10 mM) and BaCl₂ (1 mM), relatively nonspecific potassium channel antagonists, caused 50% inhibition of CGRP-induced relaxation. Glyburide (10 μM), a relatively specific antagonist of the ATP-sensitive potassium channel, caused only 22% inhibition of relaxation. Prevention of G protein activation with pertussis toxin (500 ng/ml) caused the greatest inhibition of CGRP-induced relaxation, 65%. Using the patch-clamp technique in the cell-attached configuration, CGRP added to the bath induced the activation of potassium channels of varying amplitude in isolated tail artery cells. The lack of effect of indomethacin and removal of the endothelium suggest that prostaglandins and endothelium-derived factors do not play a role in CGRP's action. The inhibitory effect of the different potassium channel antagonists and the patch-clamp data suggest that the relaxant effect of CGRP is mediated, in large part, by the activation of more than one type of potassium channel. The inhibitory effect of pertussis toxin indicates that this activation is coupled to the CGRP receptor by G proteins.