Gonzales R A, Crews F T
Department of Pharmacology, University of Florida Medical School, Gainesville.
Alcohol Alcohol Suppl. 1987;1:567-71.
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.
研究了乙醇对脑和肝切片中受体刺激的磷酸肌醇（PI）水解的影响。去甲肾上腺素（NE）用作α1 - 肾上腺素能受体激动剂，以刺激这两种组织中的PI水解。在来自大脑皮层、海马体、下丘脑和纹状体的切片中，500 mM体外乙醇可使最大浓度去甲肾上腺素（如100 μM）刺激的PI水解受到约50%的抑制。500 mM乙醇对脑干切片中NE刺激的PI水解没有影响。在500 mM乙醇存在下，上述所有脑区中KCl（20 mM）刺激的PI水解均受到强烈抑制。为了进一步表征乙醇对脑中PI水解的影响，使用了分离的膜制剂。高达500 mM的乙醇浓度对皮层膜中鸟嘌呤核苷酸和钙依赖性PI水解没有影响。在肝切片中，30 mM体外乙醇可使NE刺激的PI水解受到50%的抑制。这些结果表明，乙醇可能会干扰脑和肝中α1受体与磷酸肌醇磷酸二酯酶的偶联。
