The activities of microsomal phospholipase A2 (PLA2) and C (PLC) from mouse brain, heart and liver were determined using the substrate 1-palmitoyl-2-N-(4-nitrobenzo-2-oxa-1, 3-diazole amino caproyl-phosphatidyl-choline (NBD-PC), and the effects of chronic ethanol treatment (ethanol) as well as in vitro addition of various n-alcohols including ethanol on these activities were evaluated. Microsomal membrane fluidity was estimated by diphenylhexatriene anisotropy (γ). The microsomes from the brain and heart of ethanol-treated mice showed significantly higher PLA2 activity than those from controls. The brains of ethanol group showed significantly higher PLC activity, while, the heart showed significantly lower PLC activity than those of controls. The microsomes from the brain and heart of ethanol-treated mice showed significantly reduced γ values compared to those of controls. The addition of ethanol in vitro to microsomes was found to increase PLC activity in these tissues, while it decreased PLA2 activity in a dose-dependent manner. The other n-alcohols showed similar effects on PLA2 and PLC activity in the liver microsomes, while decreases were observed the γ values in a dose-dependent manner. These result suggest that the change in the membrane fluidity associated with adition of alcohols is a prerequisite for the changes in PLA2 and PLC activities. In addition, our findings suggest that these changes may play a major role in the cellular injury associated with chronic ethanol treatment in the mouse.
The Pharmaceutical Society of Japan