Synthesis and Action of the Cyclic AMP Antagonist, Prostaglandylinositol Cyclic Phosphate (Cyclic PIP), in Dictyostelium discoideum

摘要

The cyclic AMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), is synthesized from prostaglandin E (PGE) and activated inositol phosphate (n-IP) in the presence of ATP by an enzyme of rat liver plasma membranes. Extracts of the slime mould Dictyostelium discoideum contain this activated inositol phosphate and D. discoideum cells convert [~3H]PGE_1 to [~3H]cyclic PIP. This extracted polar [~3H]product co-chromatographed with cyclic PIP from rat liver on gel filtration, anion exchange- and adsorption chromatography. Starving D. discoideum cells show cyclic AMP-induced oscillations, which can be inhibited by cyclic PIP (0.4 * 10~(-7) M), but not by its phosphomonoester prostaglandylinositol phosphate (PIP) (1.4 * 10~(-7) M). AMP and ADP at much higher concentrations (1 mM) antagonized these oscillations. The time needed for aggregation and fruiting body formation of starving D. discoideum cells is extended by cyclic PIP (1.4 * 10~(-7) M) up to 3-fold, whereas its phosphomonoester (1.9 * 10~(-7) M) showed a 9-fold weaker effect, and AMP and ADP even at 1 mM concentration showed no effect.