ALTERATIONS IN THE STIMULATORY G-PROTEIN OF THE RAT-LIVER AFTER PARTIAL-HEPATECTOMY

In adult male rat livers, cAMP generation in response to beta-adrenerg ic agonists was dramatically stimulated after partial hepatectomy. Qua ntitation of the alpha subunits of the stimulatory G protein (G(S alph a)) using ADP-ribosylation catalyzed by cholera toxin revealed the inc rement in the amounts of two forms of G(s alpha), G(s alpha-S) and G(s alpha-L), during liver regeneration. These increases in the amounts o f both G(s alpha) proteins were associated with the stimulation in the ir mRNA levels. In addition, partial hepatectomy gave rise to a shift in the proportion of beta-adrenergic receptor (beta-AR) in the high af finity state produced by beta-AR-Gs complex. The susceptibility of G(s alpha) to trypsin was used as a probe for beta-AR-Gs coupling. The GT P-bound forms of both G(s alpha-S) and G(s alpha-L) were more trypsin- sensitive than their GDP-bound forms. Preincubation of liver plasma me mbranes prepared from partially hepatectomized rats with the agonist i soproterenol resulted in an enhancement of trypsin-sensitivity of G(s alpha-L), but not G(s alpha-S). This effect was retarded by the additi on of the antagonist propranolol. We conclude that the increase in the amount of G(s alpha) can be contributed to the rise in beta-response after partial hepatectomy, and suggest that beta-AR is preferentially coupled with G(s alpha-L) rather than G(s alpha-S).