Prostacyclin (PGI) Receptor Binding and Cyclic AMP Synthesis Activities of PGI1 Analogues, SM-10906 and Its Methyl Ester, SM-10902, in Mastocytoma P-815 Cells.

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Abstract
The prostacyclin I1 (PGI1) analogue, SM-10906 and its methyl ester, SM-10902, have been compared with the PGI2 analogue, iloprost, with respect to binding to the PGI2 receptor, stimulation of adenylate cyclase activity and inhibition of thrombin-induced Ca2+ mobilization in mastocytoma P-815 cells. SM-10906 displaced [3H]iloprost binding to the membrane fraction, the IC50 value being 100 nM, but showed very low affinity for the prostaglandin E (PGE) receptor. SM-10906 dose-dependently stimulated GTP-dependent adenylate cyclase activity in the membrane fraction, the EC50 value being 35 nM. Furthermore, SM-10906 prevented a thrombin-induced increase in the intracellular Ca2+ concentration, the IC50 value being 300 nM. These IC50 and EC50 values are much lower than those of SM-10902. These results demonstrate that SM-10906, a stable PGI1 derivative, is an agonist for the [3H]iloprost-binding (PGI2) receptor, and that it prevents thrombin-induced Ca2+ mobilization through stimulation of the adenylate cyclase system in mastocytoma cells. On the other hand, a methyl ester derivative of PGI1, SM-10902, was inactive in the binding assay, but it seems to be a partial agonist for adenylate cyclase activity [corrected].

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