sb-269970 and sarpogrelate

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