PT  - JOURNAL ARTICLE
AU  - Bhattacharya, Anindya
AU  - Schenck, Kathryn W.
AU  - Xu, Yao-Chang
AU  - Nisenbaum, Laura
AU  - Galbreath, Elizabeth
AU  - Cohen, Marlene L.
TI  - 5-Hydroxytryptamine<sub>1B</sub> Receptor-Mediated Contraction of Rabbit Saphenous Vein and Basilar Artery: Role of Vascular Endothelium
AID  - 10.1124/jpet.103.062653
DP  - 2004 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 825--832
VI  - 309
IP  - 2
4099  - http://jpet.aspetjournals.org/content/309/2/825.short
4100  - http://jpet.aspetjournals.org/content/309/2/825.full
SO  - J Pharmacol Exp Ther2004 May 01; 309
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