SYNTHESIS AND ACTION OF THE CYCLIC-AMP ANTAGONIST, PROSTAGLANDYLINOSITOL CYCLIC PHOSPHATE (CYCLIC PIP), IN DICTYOSTELIUM-DISCOIDEUM

The cyclic AMP antagonist, prostaglandylinositol cyclic phosphate (cyc lic PIP), is synthesized from prostaglandin E (PGE) and activated inos itol phosphate (n-IP) in the presence of ATP by an enzyme of rat liver plasma membranes. Extracts of the slime mould Dictyostelium discoideu m contain this activated inositol phosphate and D, discoideum cells co nvert [H-3]PGE(1) to [H-3]cyclic PIP. This extracted polar [H-3]-produ ct co-chromatographed with cyclic PIP from rat liver on gel filtration , anion exchange- and adsorption chromatography, Starving D. discoideu m cells show cyclic AMP-induced oscillations, which can be inhibited b y cyclic PIP (0.4 x 10(-7) M), but not by its phosphomonoester prostag landylinositol phosphate (PIP) (1.4 x 10(-7) M), AMP and ADP at much h igher concentrations (1 mM) antagonized these oscillations, The time n eeded for aggregation and fruiting body formation of starving D. disco ideom cells is extended by cyclic PIP (1.4 x 10(-7) M) up to 3-fold, w hereas its phosphomonoester (1.9 x 10(-7) M) showed a 9-fold weaker ef fect, and AMP and ADP even at 1 mM concentration showed no effect.