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

In a previous study, it was found thatexposure to tumor necrosis factor- (TNF-) potentiated theelectrophysiological response to carbachol in a time-dependent andcycloheximide-sensitive manner. It was deduced that the potentiationcould be due to protein kinase C activity because of increased1,2-diacylglycerol. It was also observed that propranolol coulddecrease 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 investigatewhether the phospholipase D (PLD) pathway plays a role in the carbacholresponse and the potentiating effect of TNF-. Thetransphosphatidylation reaction in the presence of the primary alcohol1-butanol [leading to stable phosphatidylbutanol (Pbut) formation]was used to measure activity of PLD. The phosphatidic acid (PA) levelswere also measured. Muscarinic stimulation resulted in an increasedformation of Pbut and PA. TNF- decreased levels of PA.