Heterologous desensitization of the liver adenylyl cyclase: analysis of the role of G-proteins

Endocrinology
R T Premont, R Iyengar

Abstract

Glucagon treatment of chick hepatocytes in primary culture results in a rapid 20-30% decrease in NaF-stimulated adenylyl cyclase activity. This heterologous desensitization is rapidly reversible upon removal of hormone from the culture medium. This decrease in NaF-stimulated adenylyl cyclase activity agrees well with the decrease in Gs activity, as assessed by reconstitution of the cyc- S49 cell adenylyl cyclase. Recovery from heterologous desensitization within 30 min results in restoration of Gs activity to control levels. No changes in Gs-alpha protein levels could be determined by immunoblotting using an alpha s-specific antiserum during heterologous desensitization. Similarly, no change in the beta gamma-subunits or Gi-alpha-subunits were detected by immunoblotting analysis using subunit-specific antisera. Pretreatment of cells with pertussis toxin did not block the onset of either heterologous or homologous desensitization, indicating the lack of involvement of Gi in glucagon-induced desensitization. cAMP-dependent phosphorylation of G-proteins does not account for heterologous desensitization, since none of the G-protein subunits appears to be phosphorylated even in vitro. However, Gs as the locus of change in heterologo...Continue Reading

Citations

Aug 1, 1993·Journal of Cellular Biochemistry·N McFarlane-AndersonN Bégin-Heick
Feb 1, 1991·Molecular and Cellular Endocrinology·B DelemerC Corrèze
Aug 30, 1995·Molecular and Cellular Endocrinology·S G Laychock
Jan 1, 1991·Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology·H FujinamiM Tsuboi
Oct 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·R T PremontR Iyengar
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·Y ChenR Iyengar
Apr 5, 2003·Biochimica Et Biophysica Acta·Ling-Chu ChangJih-Pyang Wang
May 26, 1995·The Journal of Biological Chemistry·G IwamiY Ishikawa

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