COMBINED EFFECTS OF ADRENERGIC AND INTRAVENOUS ANESTHETIC AGENTS ON INOSITOL MONOPHOSPHATE LEVELS IN RAT-LIVER PRISMS

Combined effects of adrenergic and intravenous anesthetic agents on ph osphatidylinositol (PI) turnover were studied using rat liver prisms i ncubated with [H-3]myo-inositol. Rat liver prisms responded to epineph rine, norepinephrine and phenylephrine dose-dependently with an increa se in inositol monophosphate (IP1) formation but they did not respond to ephedrine. Dopamine-induced effects were seen only at concentration s as high as 10(-4) mol . l-1. The enhancement of IP1 formation induce d by epinephrine was potentiated by thiamylal at concentrations of 10( -5) mol . l-1 and 10(-4) mol . l-1, remained unaffected by ketamine, f entanyl or midazolam, but was dose-dependently inhibited by droperidol . The present results from in vitro studies of liver cell metabolism s uggest that alpha-adrenergic agents in combination. with barbiturates may potentiate liver cell damage by activation of PI turnover and inte rrelated intracellular Ca++ accumulation.