Dual effects of ATP on phosphatidylinositol breakdown in rat hepatocyte membranes |
| |
Authors: | Javier Ibarrondo Aida Marino Gilles Guillon Miguel Trueba JosMaría Macarulla |
| |
Institution: | a Departamento de Bioquimica y Biología Molecular, Facultad de Ciencias, Universidad del Pais Vasco/ Euskal Herriko Unibertsitatea, Apdo. 644 48080, Bilbao, Spain b Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Rue de la Cardonille, 34094, Montpellier Cedex 5, France |
| |
Abstract: | The mechanisms whereby adenosine-5−triphosphate (ATP)_regulated the inositol phospholipid-signalling system were studied in rat hepatocytes. Intact hepatocytes respond to extracellular ATP, adenosine-5′-O-(3-thiotriphosphate) (ATPγS), ADP and weakly to guanosine-5′-triphosphate (GTP), but not to other purine nucleotides (GDP or AMP). This is consistent with the ideal 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, ATPγS and guanosine-5′-O-(3-thiotriphosphate) (GTPγS). Moreover the GTPγS effect of greatly enhanced by ATP and ATPγS. These potentiating effects differ according to the adenylnucleotide considered. ATP produces (1) an increase in the GTPγS-PLC sensitivity, (2) a potentiation of the phospholipase C (PLC) response induced by maximal dose of GTPγS, and (3) an increase in the inositol lipids pools. At variance, ATPγS, a nonhydrolysable analogue of ATP, only increases the PLC-sensitivity towards GTPγS. 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 phosphatidyinositol-4-phosphate (PIP) kinases which increased the pool of phospholipase C substrates. |
| |
Keywords: | Liver membranes ATP P2 receptors inositol phosphates G-protein |
本文献已被 ScienceDirect 等数据库收录! |
|