Epithio-11, 12-Methano-Thromboxane A<SUB>2</SUB> Stimulates Inositol Phosphates Accumulation in Isolated Canine Mesenteric Artery Strips
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概要
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Epithio-11, 12-methano-thromboxane A<SUB>2</SUB> (STA<SUB>2</SUB>), a stable analog of thromboxane A<SUB>2</SUB> (TXA<SUB>2</SUB>), stimulated inositol phosphates (IPs) accumulation in canine mesenteric artery strips, but not in cerebral (basilar) artery strips. When canine mesenteric artery strips were incubated with 0.1 μM [<SUP>3</SUP>H]<I>myo</I>-inositol for 15 min and then stimulated with 10 μM STA<SUB>2</SUB> for 30 min, there was a significant increase in <SUP>3</SUP>H-IPs accumulation as measured by anion exchange chromatography (2, 028 ± 204 and 3, 526 ± 210<SUP>*</SUP> dpm/mg protein for basal and stimulated accumulations, respectively; means ± S.E.M., n = 3, <SUP>*</SUP>P < 0.01, significantly different from the basal value). This effect of STA<SUB>2</SUB> was dose-dependent with an EC<SUB>50</SUB> value of 1.6 ± 0.2 μM. The presence of equimolar concentrations of TXA<SUB>2</SUB> receptor antagonists, either ONO-3708 (9, 11-dimethylmethano-11, 12-methano-13, 14-dihydro-13-aza-14-oxo-15-cyclopental-16, 17, 18, 19, 20-pentanor-15-epi-thromboxane A<SUB>2</SUB>) or S-1452 (5Z-7-(3-<I>endo</I>-phenylsulfonylamino (2.2.1.)-bicyclohept-2-<I>exo</I>-yl)heptenoic acid), completely blocked the effect of STA<SUB>2</SUB>. These results suggest the presence of TXA<SUB>2</SUB> receptors coupled with IPs accumulation in canine mesenteric artery strips. The exact location of the TXA<SUB>2</SUB> receptor-IPs system, however, remains unknown.
著者
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Fujiwara Motohatsu
Department Of Pharmacology Faculty Of Medicine Kyoto University
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Ninomiya Haruaki
Department Of Biological Regulation Faculty Of Medicine Tottori University
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Ninomiya Haruaki
Department of Neurosciences, School of Medicine, University of California
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