dinoprost has been researched along with sarpogrelate* in 2 studies
2 other study(ies) available for dinoprost and sarpogrelate
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Characteristics of the actions by which 5-HT affects electrical and mechanical activities in rabbit jugular vein.
5-HT is known to be a potent vasospasmogenic agonist in various arteries. However, in veins the vasomodulating actions of 5-HT, and the underlying mechanisms, remain to be fully clarified. Here, we characterized the actions by which 5-HT affects electrical and mechanical activities in the rabbit jugular vein.. Membrane potential and isometric tension were measured in endothelium-intact and -denuded preparations. Localization of 5-HT receptor subtypes was examined immunohistochemically.. 5-HT induced a transient then a small, sustained smooth muscle cell hyperpolarization in endothelium-intact strips. In endothelium-denuded strips, 5-HT induced only a sustained hyperpolarization, and this was changed to a depolarization by the selective 5-HT(7) receptor inhibitor SB269970. This depolarization was inhibited by the 5-HT(2A) receptor blocker sarpogrelate. 5-HT induced a relaxation of PGF(2α) -induced contracted strips that was similar in endothelium-intact and -denuded preparations. The latter relaxation was changed to contraction by SB269970 and this contraction was inhibited by sarpogrelate. Immunoreactive responses against endothelial and smooth muscle 5-HT(2A) receptors and smooth muscle 5-HT(7) receptors were identified in the vein. The 5-HT-induced relaxation of the PGF(2α) contraction was inhibited by the cAMP-dependent protein kinase inhibitor Rp-cAMPS and by the AC inhibitor SQ22536.. These results indicate that 5-HT activates both smooth muscle 5-HT(7) receptors (to produce relaxation) and smooth muscle 5-HT(2A) receptors (to produce contraction) in rabbit jugular vein. We suggest that in this particular vein, the 5-HT(2A) receptor-induced depolarization and contraction are masked by the 5-HT(7) receptor-induced responses, possibly via actions mediated by cAMP. Topics: Adenine; Animals; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dinoprost; Endothelium, Vascular; Glyburide; Immunohistochemistry; Isometric Contraction; Jugular Veins; Male; Membrane Potentials; Muscle, Smooth, Vascular; Nitric Oxide; Phenols; Rabbits; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Serotonin; Serotonin 5-HT2 Receptor Antagonists; Succinates; Sulfonamides; Vasodilation | 2011 |
Sarpogrelate, a selective 5-HT2A serotonergic receptor antagonist, inhibits serotonin-induced coronary artery spasm in a porcine model.
Serotonin is one of the most important vasoactive substances and has been implicated in the pathogenesis of coronary artery spasm and of acute coronary syndrome. We have recently demonstrated that local and long-term treatment with interleukin-1beta(IL-1beta) causes coronary arteriosclerotic changes and hyperconstrictive responses to serotonin in pigs in vivo. However, it remains to be examined which serotonergic (5-HT) receptor subtype mediates coronary spasm and whether alterations in serotonergic receptors are involved in the abnormality. In this study, we examined the inhibitory effect of sarpogrelate, a selective 5-HT2A serotonergic receptor antagonist, on the serotonin-induced coronary spasm as well as the possible alterations of serotonergic receptors in our porcine model. A segment of the porcine coronary artery was carefully dissected and aseptically wrapped with cotton mesh absorbing IL-1beta-bound microbeads from the adventitia. Two weeks after the procedure, angiographic study was performed, followed by binding assay for 5-HT1B and 5-HT2A serotonergic receptors and reverse transcription-polymerase chain reaction (RT-PCR) analysis for mRNA of those receptors. Angiographic study showed coronary vasospastic responses to serotonin at the IL-1beta-treated site. Sarpogrelate dose-dependently inhibited the serotonin-induced coronary spasm, but it did not affect the prostaglandin F2alpha-induced vasoconstriction. Radiolabeled receptor-binding assay showed that receptor affinity or receptor number of the 5-HT1B, or 5-HT2A receptors did not differ significantly between the spastic and the control sites. Furthermore, RT-PCR analysis showed that the expression of neither 5-HT2A nor 5-HT1B receptor mRNA was significantly altered at the spastic site. These results indicate that serotonin-induced coronary spasm is mediated primarily by 5-HT2A receptor in our porcine model, although the 5-HT2A receptor was not up-regulated, suggesting that alteration in the signal-transduction pathway for vascular smooth muscle contraction beyond the 5-HT2A receptor plays a primary role in the pathogenesis of coronary spasm in our porcine model. Topics: Angiography; Animals; Base Sequence; Coronary Vasospasm; Dinoprost; Disease Models, Animal; Dose-Response Relationship, Drug; In Vitro Techniques; Interleukin-1; Male; Molecular Sequence Data; Muscle Contraction; Muscle, Smooth, Vascular; Protein Binding; Receptors, Serotonin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Serotonin; Serotonin Antagonists; Succinates; Swine; Up-Regulation; Vasoconstrictor Agents | 2000 |