Epithio-11,12-methano-thromboxane A2 stimulates inositol phosphates accumulation in isolated canine mesenteric artery strips.

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 microM [3H]myo-inositol for 15 min and then stimulated with 10 microM 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 less than 0.01, significantly different from the basal value). This effect of STA2 was dose-dependent with an EC50 value of 1.6 +/- 0.2 microM. 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.