PLD pathway involved in carbachol-induced Cl- secretion: possible role of TNF-alpha.
In a previous study, it was found that exposure to tumor necrosis factor-alpha (TNF-alpha) potentiated the electrophysiological response to carbachol in a time-dependent and cycloheximide-sensitive manner. It was deduced that the potentiation could be due to protein kinase C activity because of increased 1,2-diacylglycerol. It was also observed that propranolol could decrease the electrophysiological response to carbachol (Oprins JC, Meijer HP, and Groot JA. Am J Physiol Cell Physiol 278: C463-C472, 2000). The aim of the present study was to investigate whether the phospholipase D (PLD) pathway plays a role in the carbachol response and the potentiating effect of TNF-alpha. The transphosphatidylation reaction in the presence of the primary alcohol 1-butanol [leading to stable phosphatidylbutanol (Pbut) formation] was used to measure activity of PLD. The phosphatidic acid (PA) levels were also measured. Muscarinic stimulation resulted in an increased formation of Pbut and PA. TNF-alpha decreased levels of PA.
Swammerdam Institute for Life Sciences, University of Amsterdam, P.O. Box 94084, 1090 GB Amsterdam, The Netherlands. oprins@bio.uva.nl
J C
JC
Oprins
C
C
van der Burg
H P
HP
Meijer
T
T
Munnik
J A
JA
Groot
D020001:1-Butanol / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D019852:Diacylglycerol Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000201:enzymology; D008301:Maleimides / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011744:Pyrimidinones / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D002273:Carcinogens; D002712:Chlorides; D018679:Cholinergic Agonists; D004075:Diglycerides; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D010703:Phorbol Esters; D011744:Pyrimidinones; D011976:Receptors, Muscarinic; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D020001:1-Butanol; D002217:Carbachol; C047505:R 59022; D011433:Propranolol; D019852:Diacylglycerol Kinase; D011493:Protein Kinase C; D010739:Phospholipase D; C070515:bisindolylmaleimide I