5-Hydroxytryptamine1B receptor-mediated contraction of rabbit saphenous vein and basilar artery: role of vascular endothelium.
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-HT(1D) subtype-selective agonist (human K(i) = 2.5 +/- 0.07 nM), did not contract either tissue, whereas o-methoxyphenylpiperazide derivative 4F (MPPA-4F), a 5-HT(1B) subtype-selective antagonist (human K(i) = 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-HT(1B) receptor in these blood vessels. 5-HT(1B) 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-HT(1B)-induced contraction in both tissues. Endothelial denudation or nitric-oxide synthase inhibition with N(omega) nitro-L-arginine methyl ester (L-NAME) (100 microM) increased the efficacy and potency of sumatriptan in the saphenous vein and basilar artery. Surprisingly, in endothelial-denuded vascular tissues, L-NAME (100 microM) also significantly increased the maximal 5-HT(1B) 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-HT(1B) 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.
Bhattacharya
Anindya
A
Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana, USA. anindya.bhattacharya@roche.com
Schenck
Kathryn W
KW
Xu
Yao-Chang
YC
Nisenbaum
Laura
L
Galbreath
Elizabeth
E
Cohen
Marlene L
ML
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology*; D001578:Benzopyrans / Q000494:pharmacology; D001665:Binding Sites; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D010879:Piperazines / Q000494:pharmacology; D011817:Rabbits; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018952:Antigens, CD34; D001578:Benzopyrans; C112854:PNU 109291; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D018170:Sumatriptan; D019331:NG-Nitroarginine Methyl Ester