Dissociation of the alpha-adrenergic inhibitory effects on glucagon- and secretin-stimulated bile volume and on cyclic adenosine monophosphate production in the isolated perfused rat liver.

Abstract

In the isolated perfused rat liver, glucagon increased glucose, cAMP, and bile production. Secretin increased cAMP in the effluent more and bile volume less than glucagon, but did not increase glucose output. When glucagon and secretin were infused together, the effect on cAMP was additive, but glucose output and bile volume were the same as with glucagon alone. The stimulation of bile production by glucagon was suppressed by phenylephrine but not by oxymetazoline, whereas the glucagon-induced cAMP increase in the effluent was suppressed by oxymetazoline in a dose-dependent manner, but not by phenylephrine. Glucagon-stimulated glucose output was not suppressed even when cAMP in the effluent was significantly suppressed by oxymetazoline. The secretin-induced stimulation of bile production was suppressed by phenylephrine, but not by oxymetazoline. Secretin-stimulated cAMP was suppressed more by oxymetazoline than by phenylephrine. The bile volume was not suppressed by phenylephrine alone either in the presence or in the absence of sodium taurocholate. These results indicate that the cholestatic effect of adrenergic agents is mediated by alpha 1-adrenergic receptors, whereas their cAMP suppressive effect is mediated by alpha 2-adrenergic receptors. The stimulatory effect of glucagon on cAMP production was more resistant to alpha-adrenergic agonists than to that of secretin. The dissociation by oxymetazoline of the effects of glucagon on cAMP production from its effect on glucose production is unexplained, whereas the significance of the secretin-induced increase in cAMP production is uncertain.