Acute effects of adrenaline on hepatic lipase secretion by rat hepatocytes.
Catecholamines are responsible for the daily changes in hepatic lipase (HL) expression associated with feeding and fasting. We have studied the mechanism by which adrenaline decreases HL secretion in suspensions of freshly isolated rat hepatocytes. Adrenaline acutely inhibited HL activity through activation of the alpha1-adrenergic pathway. The cells had significantly less HL activity in the presence of adrenaline versus cycloheximide, where protein de novo synthesis is completely blocked. The specific enzyme activity of secreted HL was not affected. Intracellular HL activity was decreased by adrenaline treatment. Pulse-labeling with [35S]methionine showed that de novo synthesis of the 53-kd endo-beta-N-acetylglucosaminidase H (Endo H)-sensitive HL protein was unaffected by adrenaline. During subsequent chase of the control cells, the 53-kd form was converted to a 58-kd Endo H-resistant HL protein, which was rapidly secreted into the medium. In the presence of adrenaline, formation of the 58-kd protein was markedly reduced, whereas the 53-kd protein disappeared at a rate similar to the rate in controls. This suggests that part of the HL protein was degraded. In contrast to adrenaline, inhibition of HL secretion by colchicine was accompanied by an intracellular accumulation of HL activity and of the 58-kd protein. We conclude that adrenaline inhibits HL secretion posttranslationally by retarding the maturation of the 53-kd HL precursor to an active 58-kd protein, possibly by stimulating degradation of newly synthesized HL protein.
Neve
B P
BP
Department of Biochemistry, Erasmus University Rotterdam, The Netherlands.
Verhoeven
A J
AJ
Jansen
H
H
D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004837:Epinephrine / Q000494:pharmacology*; D008049:Lipase / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000378:metabolism; D011233:Precipitin Tests; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013462:Sulfur Radioisotopes; D013997:Time Factors
D011500:Protein Synthesis Inhibitors; D013462:Sulfur Radioisotopes; D003513:Cycloheximide; D008715:Methionine; D008049:Lipase; D004837:Epinephrine