Ethanol effects on receptor activated lipid hydrolysis in brain and liver.

The effects of ethanol in receptor-stimulated phosphoinositide (PI) hydrolysis in brain and liver slices were investigated. Norepinephrine (NE) was used as an alpha 1-adrenergic receptor agonist to stimulate PI hydrolysis in both tissues. Stimulation of PI hydrolysis by maximal concentrations of norepinephrine (e.g., 100 microM) was inhibited approximately 50% by 500 mM in vitro ethanol in slices from the cerebral cortex, hippocampus, hypothalamus, and striatum. NE-stimulated PI hydrolysis was not affected by 500 mM ethanol in brain stem slices. KCl (20 mM)-stimulated PI hydrolysis was strongly inhibited in all of the above brain regions in the presence of 500 mM ethanol. To further characterize the effects of ethanol on PI hydrolysis in brain, an isolated membrane preparation was used. Guanine nucleotide and calcium-dependent PI hydrolysis in cortical membranes was not affected by concentrations of ethanol as high as 500 mM. In liver slices, NE-stimulated PI hydrolysis was inhibited 50% by 30 mM ethanol in vitro. These results suggest that ethanol may interfere with the coupling of the alpha 1 receptor to the phosphoinositide phosphodiesterase in brain and liver.