Gonzales R A, Crews F T
Department of Pharmacology, University of Florida Medical School, Gainesville.
Alcohol Clin Exp Res. 1988 Feb;12(1):94-8. doi: 10.1111/j.1530-0277.1988.tb00139.x.
The effects of ethanol on phosphoinositide (PI) hydrolysis in rat cortex and cerebellum were studied to determine if this signal transduction mechanism is a pharmacological site of action for ethanol. In addition PI responses in young adult (8 months old) and old (22 months old) rats were compared to investigate the possible interaction between chronic ethanol treatment and aging on stimulated inositide metabolism. Fischer 344 rats were maintained on a nutritionally complete liquid diet containing sucrose or ethanol for 5 months. PI hydrolysis in prelabeled cortical or cerebellar slices was determined by measuring the release of [3H]inositol phosphates in the presence of 8 mM LiCl. Neither chronic ethanol nor aging altered maximal PI responses to carbachol or submaximal responses elicited by 20 mM KCl or 30 microM A23187. The glutamate-induced response was slightly reduced in the aged rats. Concentration-effect curves for norepinephrine (NE)-stimulated PI hydrolysis were similar in sucrose- and ethanol-treated cortex and cerebellum. Ethanol in vitro inhibited NE-stimulated PI hydrolysis in cortical but not cerebellar slices. The ethanol-induced inhibition of the NE-stimulated PI response was not altered by aging or chronic ethanol treatment. These results suggest that aging or chronic ethanol treatment do not cause large changes in the responsiveness of most PI-linked receptors, and thus, any deficits caused by these conditions may not be due to functional changes in receptor-mediated PI hydrolysis.
研究了乙醇对大鼠皮层和小脑磷酸肌醇（PI）水解的影响，以确定这种信号转导机制是否为乙醇的药理学作用位点。此外，比较了年轻成年（8个月大）和老年（22个月大）大鼠的PI反应，以研究慢性乙醇处理和衰老对刺激的肌醇磷脂代谢的可能相互作用。将Fischer 344大鼠维持在含有蔗糖或乙醇的营养完全的液体饮食中5个月。通过在8 mM LiCl存在下测量[3H]肌醇磷酸的释放来测定预先标记的皮层或小脑切片中的PI水解。慢性乙醇和衰老均未改变对卡巴胆碱的最大PI反应或由20 mM KCl或30 microM A23187引起的次最大反应。老年大鼠中谷氨酸诱导的反应略有降低。去甲肾上腺素（NE）刺激的PI水解的浓度-效应曲线在蔗糖处理和乙醇处理的皮层和小脑中相似。体外乙醇抑制皮层切片中NE刺激的PI水解，但不抑制小脑切片中的水解。衰老或慢性乙醇处理不会改变乙醇诱导的对NE刺激的PI反应的抑制作用。这些结果表明，衰老或慢性乙醇处理不会导致大多数PI连接受体的反应性发生大的变化，因此，由这些情况引起的任何缺陷可能不是由于受体介导的PI水解的功能变化所致。
