title: Phospholipase D activation regulates endothelin-1 stimulation of phosphoinositide-specific phospholipase C in SK-N-MC cells.
abstract: Endothelin-1 (ET-1) is known to stimulate phospholipase C (PLC) activity in SK-N-MC human neuroblastoma/epithelioma cells: here we show that phospholipase D (PLD) is also stimulated. The generation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) by ET-1-stimulated PLC was attenuated by protein kinase C (PKC) activation and enhanced by PKC inhibition. An enhancement of ET-1-stimulated Ins(1,4,5)P3 accumulation was also seen when the product of PLD activity was either diverted into phosphatidyl butanol in the presence of butanol, or phosphatidate phosphohydrolase (PPH) activity was inhibited by DL-propranolol. We conclude that there is an inhibitory, PKC-mediated, feedback loop in these cells which is dependent, in part, on the activation of PKC by product(s) of the PLD/PPH pathway. This provides a novel role for agonist-stimulated PLD activation.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Leicester, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Challiss
authors.forename: L C
authors.initials: LC
authors.lastname: Wilkes
authors.forename: V
authors.initials: V
authors.lastname: Patel
authors.forename: J R
authors.initials: JR
authors.lastname: Purkiss
authors.forename: M R
authors.initials: MR
authors.lastname: Boarder
mesh_terms: D000440:Butanols / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D000440:Butanols; D016232:Endothelins; D007211:Indoles; D007295:Inositol Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220