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Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver.

Publication ,  Journal Article
Diehl, AM; Yang, SQ; Wolfgang, D; Wand, G
Published in: J Clin Invest
June 1992

Events leading to cAMP accumulation after partial hepatectomy (PH) and effects of cAMP on hormonal induction of DNA synthesis in hepatocytes were characterized. Hepatic cAMP peaked biphasically post-PH and paralleled changes in adenylyl cyclase activity. Fluctuations in cyclase activity were not explained by variations in glucagon receptor kinetics, but reflected altered G-protein expression. Membrane levels of the stimulatory G-protein, Gs alpha, increased early after PH and were sustained. Levels of the inhibitory G-protein, Gi2 alpha, increased more slowly, peaked later, and quickly fell. Levels of both G-proteins correlated poorly with levels of their mRNAs, suggesting posttranscriptional factors modify their membrane concentrations. When growth factor-induced DNA synthesis was compared in hepatocyte cultures grown with or without agents that increase intracellular cAMP, DNA synthesis was inhibited by sustained high levels of cAMP but was enhanced when high cAMP levels fell. In both regenerating liver and hepatocyte cultures, the expression of a "differentiated" hepatocyte gene, phosphoenolpyruvate carboxykinase, correlated with elevated cAMP levels. These data suggest that the differential expression of G-proteins integrates signals initiated by several growth factors so that the accumulation of cAMP is tightly regulated post-PH. The ensuing variations in cAMP levels modulate both growth and differentiated functions during liver regeneration.

Duke Scholars

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

June 1992

Volume

89

Issue

6

Start / End Page

1706 / 1712

Location

United States

Related Subject Headings

  • Rats, Inbred Strains
  • Rats
  • Male
  • Liver Regeneration
  • Liver
  • Kinetics
  • Immunology
  • Hepatectomy
  • GTP-Binding Proteins
  • DNA
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Diehl, A. M., Yang, S. Q., Wolfgang, D., & Wand, G. (1992). Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver. J Clin Invest, 89(6), 1706–1712. https://doi.org/10.1172/JCI115771
Diehl, A. M., S. Q. Yang, D. Wolfgang, and G. Wand. “Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver.J Clin Invest 89, no. 6 (June 1992): 1706–12. https://doi.org/10.1172/JCI115771.
Diehl AM, Yang SQ, Wolfgang D, Wand G. Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver. J Clin Invest. 1992 Jun;89(6):1706–12.
Diehl, A. M., et al. “Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver.J Clin Invest, vol. 89, no. 6, June 1992, pp. 1706–12. Pubmed, doi:10.1172/JCI115771.
Diehl AM, Yang SQ, Wolfgang D, Wand G. Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver. J Clin Invest. 1992 Jun;89(6):1706–1712.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

June 1992

Volume

89

Issue

6

Start / End Page

1706 / 1712

Location

United States

Related Subject Headings

  • Rats, Inbred Strains
  • Rats
  • Male
  • Liver Regeneration
  • Liver
  • Kinetics
  • Immunology
  • Hepatectomy
  • GTP-Binding Proteins
  • DNA