Effects of chronic exposure to ethanol alone and in combination with desipramine on beta-adrenoceptors of rat brain.
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.
Turkka
J
J
Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Gurguis
G
G
Karanian
J
J
Potter
W Z
WZ
Linnoila
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D000431:Ethanol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D003891:Desipramine