Acetate-induced adenosine mediated effects of ethanol.
Ethanol administration leads to a marked increase in hepatic blood flow, resulting from an increase in mesenteric blood flow. Studies presented indicate that the increase in portal blood flow induced by ethanol is mediated by acetate. Acetate infusion at rates which achieve blood concentrations equal to those following ethanol administration, fully reproduce this effect of ethanol. The adenosine receptor blocker 8-phenyltheophilline (8PT) fully abolishes the increase in portal blood flow induced by both ethanol and acetate. We have proposed that the extrahepatic metabolism of acetate into acetyl-CoA yields AMP and adenosine. Studies also indicate that adenosine receptor activation has a major contribution to the CNS depressant effects of ethanol at low concentrations of ethanol (below 1.5 g/kg) where the production of acetate is near maximal and the physico-chemical effects of ethanol are minor. Acetate significantly potentiates the CNS depressant effects of general anesthetics. Data to be presented indicate that for some behaviours, acetate through an adenosine-receptor activation potentiates the effects of ethanol while in other behavioural tests they antagonize ethanol effects.
Carmichael
F J
FJ
Department of Pharmacology, University of Toronto, Ontario, Canada.
Orrego
H
H
Israel
Y
Y
D000085:Acetates / Q000378:metabolism / Q000494:pharmacology*; D019342:Acetic Acid; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D000085:Acetates; D018047:Receptors, Purinergic P1; D000431:Ethanol; D000249:Adenosine Monophosphate; D000105:Acetyl Coenzyme A; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D019342:Acetic Acid