Acetate-mediated effects of ethanol.
Ethanol has been shown to increase markedly portal blood flow, primarily by increasing intestinal blood flow. This effect of ethanol is reproduced by acetate, infused at rates equivalent to those leading to endogenous acetate production following ethanol administration. The physiological mediator, adenosine, is also known to increase markedly intestinal and portal tributary blood flow. We have shown that adenosine receptor blockade with 8-phenyltheophylline completely abolishes the effects of ethanol, acetate, and adenosine on intestinal and portal blood flow, suggesting that increases in adenosine tone may constitute a common mechanism mediating the actions of both ethanol and acetate on the splanchnic vasculature. Studies are also presented that show that acetate administration has marked effects on central nervous system function. On two tests, motor coordination and anesthetic potency, both ethanol and acetate showed similar effects. The effects of acetate were fully abolished by 8-phenyltheophylline. The effects of ethanol were partially blocked by 8-phenyltheophylline, with a greater effect of this blocker being seen at low doses of alcohol. Whereas ethanol at low doses increased locomotor activity in mice, acetate markedly reduced it. The effect of acetate on locomotion was fully reversed by the adenosine receptor blocker 8-phenyltheophylline, whereas the activating effect of ethanol on locomotion was markedly enhanced by this blocker. These data suggest that the actions of ethanol on locomotor activity normally result from the combination of a direct stimulatory effect of ethanol per se and an inhibitory effect of acetate, produced endogenously from ethanol. When the latter effect of acetate is abolished by adenosine receptor blockade, the activating effect of ethanol is fully expressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Israel
Y
Y
Department of Pharmacology, University of Toronto, Ontario, Canada.
Orrego
H
H
Carmichael
F J
FJ
D000079:Acetaldehyde / Q000493:pharmacokinetics / Q000633:toxicity*; D000085:Acetates / Q000493:pharmacokinetics / Q000633:toxicity*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology
D000085:Acetates; D000431:Ethanol; D000079:Acetaldehyde