Turkka J, Gurguis G, Karanian J, Potter W Z, Linnoila M
Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Eur J Pharmacol. 1990 Feb 27;177(3):171-9. doi: 10.1016/0014-2999(90)90267-a.
The effect of chronic ethanol exposure alone or in combination with desipramine on agonist and antagonist binding to beta-adrenoceptors was studied in membrane preparations from rat frontal cortex and hippocampus. Ten day exposure of animals to ethanol vapor (25 mg/l) in inhalation chambers had no effect on binding properties of antagonist iodocyanopindolol (ICYP) in either brain region. However, ethanol in combination with chronic desipramine treatment prevented the reduction of beta-adrenoceptor density in frontal cortex produced by desipramine administration. Similar to its effects on antagonist binding, chronic ethanol exposure did not change the agonist isoproterenol binding characteristics measured in membranes from either rat frontal cortex or hippocampus. However, the combination of ethanol plus desipramine reduced the dissociation constant of the low affinity state of the receptor (KL) in frontal cortex from 23.1 +/- 3.7 microM in controls to 11.2 +/- 1.7 microM. Moreover, ethanol plus desipramine produced a greater decrease in the percentage of cortical receptors in the high affinity state for agonist (%RH) than did desipramine alone. This suggests that ethanol enhances desipramine-induced desensitization of beta-adrenoceptors in frontal cortex in spite of the prevention of reduction in density of the receptors. In hippocampal membranes, ethanol together with desipramine prevented desipramine-induced changes in agonist binding characteristics, i.e. the decrease in KH (dissociation constant from high affinity state of the receptor) and the consequent enhancement in KL/KH ratio. Thus, chronic exposure to relatively low concentrations of ethanol partially prevents effects of desipramine on beta-adrenoceptors.
研究了单独慢性乙醇暴露或乙醇与地昔帕明联合使用对大鼠额叶皮质和海马膜制剂中激动剂和拮抗剂与β-肾上腺素能受体结合的影响。将动物在吸入室中暴露于乙醇蒸气（25mg/l）10天，对任一脑区拮抗剂碘氰吲哚洛尔（ICYP）的结合特性均无影响。然而，乙醇与慢性地昔帕明治疗联合使用可防止地昔帕明给药导致的额叶皮质β-肾上腺素能受体密度降低。与对拮抗剂结合的影响相似，慢性乙醇暴露并未改变在大鼠额叶皮质或海马膜中测得的激动剂异丙肾上腺素的结合特性。然而，乙醇加地昔帕明可使额叶皮质中受体低亲和力状态的解离常数（KL）从对照组的23.1±3.7μM降至11.2±1.7μM。此外，乙醇加地昔帕明比单独使用地昔帕明使激动剂高亲和力状态下皮质受体的百分比（%RH）下降幅度更大。这表明，尽管防止了受体密度降低，但乙醇仍增强了地昔帕明诱导的额叶皮质β-肾上腺素能受体脱敏。在海马膜中，乙醇与地昔帕明联合使用可防止地昔帕明诱导的激动剂结合特性变化，即KH（受体高亲和力状态的解离常数）降低以及KL/KH比值随之升高。因此，长期暴露于相对低浓度的乙醇可部分防止地昔帕明对β-肾上腺素能受体的影响。
