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

In adult male rat livers, cAMP generation in response to beta-adrenergic agonists was dramatically stimulated after partial hepatectomy. Quantitation of the alpha subunits of the stimulatory G protein (G(S alpha)) using ADP-ribosylation catalyzed by cholera toxin revealed the increment 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 of both G(s alpha) proteins were associated with the stimulation in their mRNA levels. In addition, partial hepatectomy gave rise to a shift in the proportion of beta-adrenergic receptor (beta-AR) in the high affinity 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 GTP-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 membranes prepared from partially hepatectomized rats with the agonist isoproterenol resulted in an enhancement of trypsin-sensitivity of G(s alpha-L), but not G(s alpha-S). This effect was retarded by the addition 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).