ACETATE-MEDIATED EFFECTS OF ETHANOL

Ethanol has been shown to increase markedly portal blood flow, primari ly by increasing intestinal blood flow. This effect of ethanol is repr oduced by acetate, infused at rates equivalent to those leading to end ogenous acetate production following ethanol administration. The physi ological mediator, adenosine, is also known to increase markedly intes tinal and portal tributary blood flow. We have shown that adenosine re ceptor blockade with 8-phenyltheophylline completely abolishes the eff ects of ethanol, acetate, and adenosine on intestinal and portal blood flow, suggesting that increases in adenosine tone may constitute a co mmon mechanism mediating the actions of both ethanol and acetate on th e splanchnic vasculature. Studies are also presented that show that ac etate administration has marked effects on central nervous system func tion. On two tests, motor coordination and anesthetic potency, both et hanol and acetate showed similar effects. The effects of acetate were fully abolished by 8-phenyltheophylline. The effects of ethanol were p artially blocked by 8-phenyltheophylline, with a greater effect of thi s blocker being seen at low doses of alcohol. Whereas ethanol at low d oses increased locomotor activity in mice, acetate markedly reduced it . The effect of acetate on locomotion was fully reversed by the adenos ine receptor blocker 8-phenyltheophylline, whereas the activating effe ct of ethanol on locomotion was markedly enhanced by this blocker. The se data suggest that the actions of ethanol on locomotor activity norm ally result from the combination of a direct stimulatory effect of eth anol per se and an inhibitory effect of acetate, produced endogenously from ethanol. When the latter effect of acetate is abolished by adeno sine receptor blockade, the activating effect of ethanol is fully expr essed. These data demonstrate that acetate is not an inert molecule an d that some actions of ethanol may be partially or fully mediated by a cetate.