Adenine nucleotides modulate phosphatidylcholine metabolism in aortic endothelial cells

✍ Scribed by Sabine Pirotton; Bernard Robaye; Christian Lagneau; Jean-Marie Boeynaems

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 1002 KB
• Volume: 142
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041420303

✦ Synopsis

Abstract

ATP and ADP, in concentrations ranging from 1—100 μM, increased the release of [^3^H]choline and [^3^H]phosphorylcholine (P‐choline) from bovine aortic endothelial cells (BAEC) prelabelled with [^3^H]choline. This action was detectable within 5 minutes and was maintained for at least 40 minutes. ATP and ADP were equiactive, and their action was mimicked by their phosphorothioate analogs (ATP‐γS and ADPβS) and adenosine 5′‐(β,γ imido) triphosphate (APPNP), but not by AMP, adenosine, and adenosine 5‐(α,β methylene)triphosphate (APCPP): these results are consistent with the involvement of P~2Y~ receptors. ATP also induced an intracellular accumulation of [^3^H]choline: the intracellular level of [^3^H]choline was increased 30 seconds after ATP addition and remained elevated for a least 20 minutes. The action of ATP on the release of choline metabolites was reproduced by bradykinin (1 μM), the tumor promoter phorbol 12‐myristate 13‐acetate (PMA, 50 nM), and the calcium ionophore A23187 (0.5 μM). Down‐regulation of protein kinase C, following a 24‐hour exposure of endothelial cells to PMA, abolished the effects of PMA and ATP on the release of choline and P‐choline, whereas the response to A23187 was maintained. These results suggest that in aortic endothelial cells, ATP produces a sustained activation of a phospholipase D hydrolyzing phosphatidylcholine. The resulting accumulation of phosphatidic acid might have an important role in the modulation of endothelial cell function by adenine nucleotides. Stimulation of phospholipase D appears to involve protein kinase C, activated following the release of diacylglycerol from phosphatidylinositol bisphosphate by a phospholipase C coupled to the P~2Y~ receptors (Pirotton et al., 1987a).