PMID- 1664738 OWN - NLM STAT- MEDLINE DCOM- 19920320 LR - 20190918 IS - 0898-6568 (Print) IS - 0898-6568 (Linking) VI - 3 IP - 6 DP - 1991 TI - Dual effects of ATP on phosphatidylinositol breakdown in rat hepatocyte membranes. PG - 577-85 AB - The mechanisms whereby adenosine-5'-triphosphate (ATP) regulates the inositol phospholipid-signalling system were studied in rat hepatocytes. Intact hepatocytes respond to extracellular ATP, adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S), ADP and weakly to guanosine-5'-triphosphate (GTP), but not to other purine nucleotides (GDP or AMP). This is consistent with the idea that a P2 purinergic receptor is coupled to the phosphatidylinositol metabolism in these cells. Partially purified plasma membranes prepared from myo-[3H]inositol prelabelled hepatocytes exhibit a phosphatidylinositol-4,5-bisphosphate phospholipase C activity sensitive to ATP, ATP gamma S and guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S). Moreover the GTP gamma S effect is greatly enhanced by ATP and ATP gamma S. These potentiating effects differ according to the adenylnucleotide considered. ATP produces (1) an increase in the GTP gamma S-PLC sensitivity, (2) a potentiation of the phospholipase C (PLC) response induced by maximal dose of GTP gamma S, and (3) an increase in the inositol lipids pools. At variance, ATP gamma S, a nonhydrolysable analogue of ATP, only increases the PLC-sensitivity towards GTP gamma S. These results may signify that ATP stimulates inositol phosphate accumulation via at least two distinct mechanisms (i) a direct activation of a P2 purinergic receptor coupled to a PLC via a GTP binding protein and (ii) a stimulation of the phosphatidylinositol (PI) and phosphatidylinositol-4-phosphate (PIP) kinases which increased the pool of phospholipase C substrates. FAU - Ibarrondo, J AU - Ibarrondo J AD - Departamento de Bioquimica y Biologia Molecular, Facultad de Ciencias, Universidad del Pais Vasco/Euskal Herriko Unibertsitatea, Bilabo, Spain. FAU - Marino, A AU - Marino A FAU - Guillon, G AU - Guillon G FAU - Trueba, M AU - Trueba M FAU - Macarulla, J M AU - Macarulla JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 0 (Phosphatidylinositols) RN - 35094-46-3 (adenosine 5'-O-(3-thiotriphosphate)) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - 86-01-1 (Guanosine Triphosphate) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 3.1.4.- (Type C Phospholipases) SB - IM MH - Adenosine Triphosphate/analogs & derivatives/*pharmacology MH - Animals MH - Cell Membrane/drug effects/metabolism MH - Enzyme Activation MH - Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology MH - Guanosine Triphosphate/pharmacology MH - Liver/cytology/drug effects/*metabolism MH - Male MH - Phosphatidylinositols/*metabolism MH - Rats MH - Rats, Inbred Strains MH - Type C Phospholipases/*metabolism EDAT- 1991/01/01 00:00 MHDA- 1991/01/01 00:01 CRDT- 1991/01/01 00:00 PHST- 1991/01/01 00:00 [pubmed] PHST- 1991/01/01 00:01 [medline] PHST- 1991/01/01 00:00 [entrez] AID - 0898-6568(91)90034-R [pii] AID - 10.1016/0898-6568(91)90034-r [doi] PST - ppublish SO - Cell Signal. 1991;3(6):577-85. doi: 10.1016/0898-6568(91)90034-r.