RT Journal Article
SR Electronic
T1 5-Hydroxytryptamine<sub>1B</sub> Receptor-Mediated Contraction of Rabbit Saphenous Vein and Basilar Artery: Role of Vascular Endothelium
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 825
OP 832
DO 10.1124/jpet.103.062653
VO 309
IS 2
A1 Bhattacharya, Anindya
A1 Schenck, Kathryn W.
A1 Xu, Yao-Chang
A1 Nisenbaum, Laura
A1 Galbreath, Elizabeth
A1 Cohen, Marlene L.
YR 2004
UL http://jpet.aspetjournals.org/content/309/2/825.abstract
AB This study characterizes the sumatriptan-sensitive [5-hydroxytryptamine (5-HT)1B/1D] receptor in rabbit saphenous vein and basilar artery. (S)-(-)-1-{2-[4-(4-Methoxy-phenyl)-piperazin-1-yl]-ethyl}-isochroman-6-carboxylic acid methylamide (PNU-109291), a 5-HT1D subtype-selective agonist (human Ki = 2.5 ± 0.07 nM), did not contract either tissue, whereas o-methoxyphenylpiperazide derivative 4F (MPPA-4F), a 5-HT1B subtype-selective antagonist (human Ki = 4.6 ± 0.6 nM) potently inhibited sumatriptan-induced contraction in the saphenous vein and basilar artery. These results suggested that sumatriptan-induced contraction was mediated via the 5-HT1B receptor in these blood vessels. 5-HT1B receptor-mediated contraction was then compared in endothelium-intact and denuded vessels to evaluate the role of the endothelium in regulating sumatriptan-induced contractility in these tissues. The presence of an intact endothelium inhibited 5-HT1B-induced contraction in both tissues. Endothelial denudation or nitric-oxide synthase inhibition with Nω nitro-l-arginine methyl ester (l-NAME) (100 μM) increased the efficacy and potency of sumatriptan in the saphenous vein and basilar artery. Surprisingly, in endothelial-denuded vascular tissues, l-NAME (100 μM) also significantly increased the maximal 5-HT1B receptor-induced contraction in both tissues, with no effect on potency of sumatriptan. The effect of l-NAME after endothelial denudation may reflect the presence of a low density of residual endothelial cells as estimated by CD31 antibody staining combined with the modulating effect of nitric oxide released from nonendothelial cells in vascular tissue. Endothelial modulation was specific to 5-HT1B receptors because removal of the endothelium did not significantly alter contraction to norepinephrine, histamine, prostaglandin, or potassium chloride in the saphenous vein or basilar artery. The American Society for Pharmacology and Experimental Therapeutics