Epithio-11, 12-Methano-Thromboxane A₂ Stimulates Inositol Phosphates Accumulation in Isolated Canine Mesenteric Artery Strips

Abstract

Epithio-11, 12-methano-thromboxane A₂ (STA₂), a stable analog of thromboxane A₂ (TXA₂), 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 [³H]myo-inositol for 15 min and then stimulated with 10 μM STA₂ for 30 min, there was a significant increase in ³H-IPs accumulation as measured by anion exchange chromatography (2, 028 ± 204 and 3, 526 ± 210^* dpm/mg protein for basal and stimulated accumulations, respectively; means ± S.E.M., n = 3, ^*P < 0.01, significantly different from the basal value). This effect of STA₂ was dose-dependent with an EC₅₀ value of 1.6 ± 0.2 μM. The presence of equimolar concentrations of TXA₂ 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 A₂) or S-1452 (5Z-7-(3-endo-phenylsulfonylamino (2.2.1.)-bicyclohept-2-exo-yl)heptenoic acid), completely blocked the effect of STA₂. These results suggest the presence of TXA₂ receptors coupled with IPs accumulation in canine mesenteric artery strips. The exact location of the TXA₂ receptor-IPs system, however, remains unknown.