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 (Gs alpha) using ADP-ribosylation catalyzed by cholera toxin revealed the increment in the amounts of two forms of Gs alpha, Gs alpha-S and Gs alpha-L, during liver regeneration. These increases in the amounts of both Gs 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 Gs alpha to trypsin was used as a probe for beta-AR-Gs coupling. The GTP-bound forms of both Gs alpha-S and Gs 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 Gs alpha-L, but not Gs alpha-S. This effect was retarded by the addition of the antagonist propranolol. We conclude that the increase in the amount of Gs alpha can be contributed to the rise in beta-response after partial hepatectomy, and suggest that beta-AR is preferentially coupled with Gs alpha-L rather than Gs alpha-S.
Yagami
T
T
Shionogi Research Laboratories, Shionogi and Co. Ltd., Osaka, Japan.
Kirita
S
S
Matsushita
A
A
Kawasaki
K
K
Mizushima
Y
Y
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006498:Hepatectomy; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D014357:Trypsin
D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; D002772:Cholera Toxin; D014357:Trypsin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol