Actions of ethanol and acetate on rat cortical neurons: ethanol/adenosine interactions.
Recent studies have suggested that ethanol may exert some of its central depressant actions by increasing the extracellular levels of adenosine in the brain. Ethanol can inhibit the cellular uptake of adenosine, thus increasing its extracellular concentration. After ethanol metabolism by the liver, blood acetate levels are elevated and acetate metabolism in the brain could also lead to the production of adenosine. Rat cerebral cortical cup release experiments failed to reveal any elevation in the extracellular levels of either adenosine or inosine following the intraperitoneal (IP) administration of ethanol (1.5 g/kg) or acetate (2 g/kg). IP-administered ethanol (0.5 and 1.0 g/kg) enhanced the magnitude and duration of the inhibition by iontophoretically applied adenosine of the spontaneous firing of rat cerebrocortical neurons; an action which would be consistent with the block of adenosine uptake. Acetate, applied iontophoretically, depressed the spontaneous firing of 63% of the cerebrocortical neurons tested. 8-p-Sulphophenyltheophylline, an adenosine antagonist, was ineffective at blocking these inhibitions, indicating that adenosine generation is unlikely to have played a major role in the acetate-evoked depression of cerebral cortical neurons.
Phillis
J W
JW
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201.
O'Regan
M H
MH
Perkins
L M
LM
D000085:Acetates / Q000494:pharmacology*; D019342:Acetic Acid; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011687:Purines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000085:Acetates; D011687:Purines; D000431:Ethanol; D000241:Adenosine; D019342:Acetic Acid; C030985:purine