Effect of phenylarsine oxide on hepatic alpha 1-adrenoreceptor responsiveness. Dissociation between ionotropic and metabolic responses.

ABSTRACT

The present studies analyze the effect of the tervalent arsenical compound phenylarsine oxide (PAO) on hepatic response to alpha 1-adrenoreceptor stimulation. PAO, while not significantly altering the rate of glycogen breakdown, was found to inhibit many characteristic alpha 1-adrenoreceptor mediated responses including H+ and Ca2+ release, increased energy production, and vascular smooth muscle contraction. PAO inhibited basal gluconeogenesis but failed to inhibit the alpha 1-agonist induced stimulation of glucose production. These data suggest that alpha 1-adrenoreceptor mediated stimulation of metabolism and rates of ion flux across the plasma membrane are separate processes and that exchange in ion homeostasis is not essential to elicit the receptor-mediated metabolic responses. The selective effect of PAO offers an interesting tool for studying the alpha 1-adrenoreceptor signaling mechanisms.