PMID- 1333251 OWN - NLM STAT- MEDLINE DCOM- 19930104 LR - 20181130 IS - 0934-9820 (Print) IS - 0934-9820 (Linking) VI - 5 Suppl DP - 1992 TI - Functionally diverse purinergic P2Y-receptors mediate prostanoid synthesis in cultured rat astrocytes: the role of ATP-induced phosphatidyl-inositol breakdown. PG - S19-22 AB - Cultured rat astrocytes possess purinergic P2Y-receptors. Stimulation of these receptors with ATP (10(-3) M) results in increased phosphatidylinositol biphosphate (PIP2)-breakdown and prostanoid formation. We have investigated the relevance of the PIP2-pathway in prostanoid synthesis. The intracellular Ca(2+)-mobilizing agent thapsigargin (TG) (10(-6) M) and the diacylglycerol (DAG)-mimetic tetradecaoylphorbol acetate (TPA) (10(-8)-10(-6) M) both stimulate prostaglandin D2 production. ATP-induced prostanoid formation can be mimicked by combined addition of TG and TPA, suggesting the importance of the second messengers IP3 and DAG, generated during P2Y-receptor mediated PIP2-breakdown. Inhibition of ATP-induced PIP2-hydrolysis by TPA (IC50 about 5 x 10(-8) M) or by 10(-4) M neomycine, however, does not affect astroglial prostanoid synthesis, showing that P2Y-receptor mediated prostanoid formation may occur also in the absence of PIP2-hydrolysis. These findings suggest that additional postreceptor mechanisms exist in the signal transduction chain of ATP-induced astroglial prostanoid synthesis. A possible involvement of phospholipase A2 and/or of Ca(2+)-channels, directly coupled to P2Y-receptors is proposed. FAU - Seregi, A AU - Seregi A AD - Department of Pharamcology, University of Freiburg, FRG. FAU - Doll, S AU - Doll S FAU - Schobert, A AU - Schobert A FAU - Hertting, G AU - Hertting G LA - eng PT - Journal Article PL - Germany TA - Eicosanoids JT - Eicosanoids JID - 8906009 RN - 0 (Phosphatidylinositol 4,5-Diphosphate) RN - 0 (Phosphatidylinositols) RN - 0 (Prostaglandins) RN - 0 (Receptors, Purinergic) RN - 0 (Terpenes) RN - 67526-95-8 (Thapsigargin) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - I16QD7X297 (Neomycin) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - RXY07S6CZ2 (Prostaglandin D2) SB - IM MH - Adenosine Triphosphate/*pharmacology MH - Animals MH - Astrocytes/drug effects/*metabolism MH - Cells, Cultured MH - Neomycin/pharmacology MH - Phosphatidylinositol 4,5-Diphosphate MH - Phosphatidylinositols/*metabolism MH - Prostaglandin D2/biosynthesis MH - Prostaglandins/*biosynthesis MH - Rats MH - Receptors, Purinergic/drug effects/*physiology MH - Terpenes/pharmacology MH - Tetradecanoylphorbol Acetate/pharmacology MH - Thapsigargin EDAT- 1992/01/01 00:00 MHDA- 1992/01/01 00:01 CRDT- 1992/01/01 00:00 PHST- 1992/01/01 00:00 [pubmed] PHST- 1992/01/01 00:01 [medline] PHST- 1992/01/01 00:00 [entrez] PST - ppublish SO - Eicosanoids. 1992;5 Suppl:S19-22.