Hepatocyte β-adrenergic responsiveness and guanine nucleotide-binding regulatory proteins

Hepatocytes isolated from hypothyroid, adrenalectomized, or partially hepatectomized rats display an enhanced β-adrenergic responsiveness as compared with cells from control animals. The enhanced β-adrenergic responsiveness is evidenced by both increased ureagenesis and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in response to isoproterenol. The role of stimulatory guanine nucleotide-binding protein (G(s)) and inhibitory guanine nucleotide-binding protein (G(i)) in the enhanced responsiveness was studied. It was observed, contrary to what would have been anticipated, that the level of G(s) [as reflected by cholera toxin-catalyzed ADP ribosylation, 5'-guanosine γ-thiotriphosphate (GTPγS)-stimulated adenylate cyclase activity, and a functional reconstitution assay] was decreased in liver membranes from adrenalectomized and partially hepatectomized rats as compared with the controls. Furthermore, the level of G(i) was increased in these conditions as reflected by pertussis toxin-catalyzed ADP ribosylation. The data suggest that changes in β-adrenergic receptor levels rather than the levels of guanine nucleotide-binding (G) regulatory proteins predominate in regulation of hepatic β-adrenergic responses by hypothyroidism, adrenalectomy, or partial hepatectomy.