This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by PREMONT, R. T. Articles by IYENGAR, R. Search for Related Content PubMed PubMed Citation Articles by PREMONT, R. T. Articles by IYENGAR, R.

Heterologous Desensitization of the Liver Adenylyl Cyclase: Analysis of the Role of G-Proteins^*

RICHARD T. PREMONT and RAVI IYENGAR

Department of Pharmacology, Mount Sinai School of Medicine of the City University of New York New York, New York 10029

Address all correspondence and requests for reprints to: Dr. Ravi Iyengar, Department of Pharmacology, Box 1215, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029.

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 G_s activity to control levels. No changes in Gs- protein levels could be determined by immunoblotting using an _s-specific antiserum during heterologous desensitization. Similarly, no change in the β-subunits or G_i--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 G_i 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, G_s as the locus of change in heterologous desensitization was confirmed by the observation that addition of purified Gs to desensitized cell membranes results in enhancement of NaF-stimulated adenylyl cyclase activity. From these data we conclude that postreceptor heterologous desensitization in chick hepatocytes results from a reversible decrease in G_s activity in the cell surface membrane.

Footnotes

^* This work was supported by NIH Grants CA-44948 and DK-38761.

Recipient of a NSF Predoctoral Fellowship.

Received March 28, 1989.

This article has been cited by other articles:

				Y. Chen, A. Harry, J. Li, M. J. Smit, X. Bai, R. Magnusson, J. P. Pieroni, G. Weng, and R. Iyengar Adenylyl cyclase 6 is selectively regulated by protein kinase A phosphorylation in a region involved in Galpha s stimulation PNAS, December 9, 1997; 94(25): 14100 - 14104. [Abstract] [Full Text] [PDF]

				G. Iwami, J.-i. Kawabe, T. Ebina, P. J. Cannon, C. J. Homcy, and Y. Ishikawa Regulation of Adenylyl Cyclase by Protein Kinase A J. Biol. Chem., May 26, 1995; 270(21): 12481 - 12484. [Abstract] [Full Text] [PDF]