Protein kinase C stimulates PtdIns-4,5-P2-phospholipase C activity.
The tumour promoter, phorbol ester 12,13-dibutyrate (PDBu), acts on rectal palisadic epithelial cells and mimics the effects of neuroparsin, an antidiuretic neuronal hormone isolated from nervous lobes of the African locust corpora cardiaca. PDBu stimulated Ca2+-dependent phospholipase C (PLC) activity resulting in inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) production, increased cytosolic free calcium (monitored with the probe indo-1) and rectal fluid resorption. A 15-min pre-treatment with polymyxin B (PMXB), a protein kinase C (PKC) inhibitor acting at the phosphatidylserine (PS) binding site, suppressed PDBu stimulatory effects on free calcium entry and fluid resorption but not on phosphatidylinositol 4, 5-bisphosphate (PtdIns-4,5-P2) breakdown. On the contrary, bisindolylmaleimide Ro 32-0432 (which inhibits PKC at its ATP binding site) abolished entirely PDBu-stimulated PLC activity. It was concluded that two PKC are involved in transduction of the antidiuretic signal of neuroparsin. One PKC is PMXB sensitive and stimulates biological response after cytosolic free Ca2+ increase, while another PKC, insensitive to the PKC inhibitor, regulates the processes induced by the former PKC. Since PMXB-insensitive PKC exerts a stimulatory effect on PtdIns-4,5-P2-PLC production, this original mechanism may be considered as a new signalling pathway under control of PKC.
CNRS UPRESA 5017, Laboratoire de Physiopathologie et Pharmacologie Vasculaire, Université Bordeaux II Victor Segalen, 146 rue Léo Saignat, 33076, Bordeaux Cedex, France.
D
D
Radallah
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Nogaro
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B
Fournier
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism; D006110:Grasshoppers; D007301:Insect Hormones; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D011112:Polymyxin B / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*
D007301:Insect Hormones; D019269:Phosphatidylinositol 4,5-Diphosphate; C058919:neuroparsin A; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D011112:Polymyxin B; D002118:Calcium