PLD pathway involved in carbachol-induced Cl- secretion: possible role of TNF-alpha

Am J Physiol Cell Physiol. 2001 Apr;280(4):C789-95. doi: 10.1152/ajpcell.2001.280.4.C789.

Abstract

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.

MeSH terms

  • 1-Butanol / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Carbachol / pharmacology*
  • Carcinogens / pharmacology
  • Chlorides / metabolism*
  • Cholinergic Agonists / pharmacology*
  • Chromatography, Thin Layer
  • Diacylglycerol Kinase / antagonists & inhibitors
  • Diacylglycerol Kinase / metabolism
  • Diglycerides / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • HT29 Cells
  • Humans
  • Indoles / pharmacology
  • Intestinal Mucosa / enzymology
  • Maleimides / pharmacology
  • Phorbol Esters / pharmacology
  • Phospholipase D / metabolism*
  • Propranolol / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Pyrimidinones / pharmacology
  • Receptors, Muscarinic / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Thiazoles / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Adrenergic beta-Antagonists
  • Carcinogens
  • Chlorides
  • Cholinergic Agonists
  • Diglycerides
  • Enzyme Inhibitors
  • Indoles
  • Maleimides
  • Phorbol Esters
  • Pyrimidinones
  • Receptors, Muscarinic
  • Thiazoles
  • Tumor Necrosis Factor-alpha
  • 1-Butanol
  • Carbachol
  • R 59022
  • Propranolol
  • Diacylglycerol Kinase
  • Protein Kinase C
  • Phospholipase D
  • bisindolylmaleimide I