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 phosphatidylinositol (PI) turnover were studied using rat liver prisms incubated with [3H]myo-inositol. Rat liver prisms responded to epinephrine, norepinephrine and phenylephrine dose-dependently with an increase in inositol monophosphate (IP1) formation but they did not respond to ephedrine. Dopamine-induced effects were seen only at concentrations as high as 10(-4) mol.l-1. The enhancement of IP1 formation induced by epinephrine was potentiated by thiamylal at concentrations of 10(-5) mol.l-1 and 10(-4) mol.l-1, remained unaffected by ketamine, fentanyl or midazolam, but was dose-dependently inhibited by droperidol. The present results from in vitro studies of liver cell metabolism suggest that alpha-adrenergic agents in combination with barbiturates may potentiate liver cell damage by activation of PI turnover and interrelated intracellular Ca++ accumulation.