Effect of 7-fluoro prostacyclin, a stable prostacyclin analogue, on cAMP accumulation and prostaglandin binding in mastocytoma P-815 cells.
The effect of 7-fluoro prostacyclin (PGI2-F), a chemically stable analogue of prostacyclin, on cAMP accumulation in and [3H]PGE binding to mastocytoma P-815 cells was compared with those of the Na salt and methyl ester of prostacyclin (PGI2-Na or PGI2-Me), which are rapidly inactivated in aqueous solution or metabolized in the tissue. PGI-F was as effective as PGI2-Me, and slightly less effective than PGI2-Na in stimulating cAMP accumulation in mastocytoma cells and rabbit platelets. PGI2-F was also more stable than PGI2-Me or PGI2-Na, and retained its original cAMP elevating activity even after incubation with or without cells for 4 h at 37 degrees C. Cells which had been exposed to PGI2-F and then washed free of unbound reagent continued to produce cAMP for more than 3 h. PGI2-F was also as effective as PGE1 or PGE2 in displacing [3H]PGE2 bound to the cells. Non-competitive inhibition by PGI2-F or PGI2-Me of [3H]PGE2 binding to the cells, with apparent Kis of 1.29 microM and 1.13 microM, respectively, indicates the presence of different receptors for PGE2 and for PGI2-F or PGI2-Me in mastocytoma P-815 cells.
D000818:Animals; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000378:metabolism*; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D012515:Mast-Cell Sarcoma / Q000378:metabolism*; D051379:Mice; D011458:Prostaglandins E / Q000378:metabolism*
D011458:Prostaglandins E; C038499:prostaglandin I2 methyl ester; C040805:7-fluoroprostacyclin; D011464:Epoprostenol; D000242:Cyclic AMP