Enhancement in beta-adrenergic responsiveness of adenylate cyclase in rat liver during regeneration after carbon tetrachloride administration.
The increased ability of rat liver to respond to beta-adrenergic stimulation has been reported under several conditions which are generally associated with enhanced proliferation of hepatocytes. In the present study we examined beta-adrenergic responsiveness of adenylate cyclase (AC) during liver regeneration after carbon tetrachloride (CCl4) intoxication. Cyclic AMP accumulation in response to isoproterenol was significantly enhanced in the liver at 48 hours after CCl4 administration. Isoproterenol-stimulated AC activity was also potentiated in crude membranes from CCl4-treated rats. Beta-adrenergic receptor density and dissociation constant, estimated from Scatchard analysis of [125I]iodopindolol binding, were unchanged in membranes from control and CCl4-treated rats. AC activity stimulated with 5'-guanylyl imidodiphosphate (GppNHp) or NaF was augmented in the intoxicated rats. Furthermore, the concentration of GppNHp required for half-maximal activation (EC50) of the enzyme was significantly decreased in CCl4-treated rats. The MnCl2-stimulated activity in CCl4-treated rats did not differ from that in control. There was no appreciable difference between the pattern of autoradiographs of ADP-ribosylation by pertussis toxin or cholera toxin obtained from control and that from CCl4-treated rats. These data indicate that the ability of AC in response to beta-adrenergic stimulation in rat liver is enhanced during the process of regeneration after CCl4 treatment and that the increased function of Gs protein possibly participates in the potentiation of the responsiveness of AC.
Hatta
S
S
Department of Pharmacology, Sapporo Medical College, Japan.
Ohshika
H
H
D000262:Adenylyl Cyclases / Q000096:biosynthesis*; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013997:Time Factors
D011943:Receptors, Adrenergic, beta; D004247:DNA; D002251:Carbon Tetrachloride; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol