Preferential suppression of insulin-stimulated proliferation of cultured hepatocytes by somatostatin: evidence for receptor-mediated growth regulation.
The role of somatostatin (SS-14) in the regulation of rat liver regeneration was examined by using thymidine incorporation into hepatocyte DNA labeled with tritiated thymidine, a nuclear-labeling index, and the binding of 125I-tyr11-SS-14 to hepatocytes isolated at various times after partial hepatectomy. The data demonstrated no suppressive effect of SS-14 on insulin and glucagon-stimulated thymidine incorporation into hepatocyte DNA as early as 2 h after partial hepatectomy. These data were substantiated by a nuclear labeling index studies. At 2 h, 125I-tyr11-SS-14 binding to its specific sites on isolated hepatocytes was undetectable. There was a time-dependent increase in binding of 125I-tyr11-SS-14 to hepatocytes obtained at various times after partial hepatectomy. There was a significant decrease in the number of binding sites after partial hepatectomy as determined by Scatchard analysis. The data were supported by autoradiography analysis of affinity labeled 125I-tyr11-SS-14-binding protein complex followed by SDS-PAGE. SS-14 also inhibited intracellular cAMP in hepatocytes obtained at 18 h after hepatectomy. The data are consistent with the hypothesis that SS-14 participates via its own receptor in the regulation of the liver regeneration.
Department of Ophthalmology, University of Michigan Medical Center, Ann Arbor 48109-0714, USA.
P C
PC
Kothary
N
N
Kokudo
F E
FE
Eckhauser
J
J
DelValle
S E
SE
Raper
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D007329:Insulin Antagonists / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000502:physiology*; D012016:Reference Values; D013004:Somatostatin / Q000494:pharmacology*
D007329:Insulin Antagonists; D017481:Receptors, Somatostatin; D013004:Somatostatin