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PMID: 214785 Published · ppublish English Journal Article

Adenosine analogs inhibit adipocyte adenylate cyclase by a GTP-dependent process: basis for actions of adenosine and methylxanthines on cyclic AMP production and lipolysis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 75 ·No. 11 ·1978-11-00 ·Pages 5362-6

Londos C, Cooper DM, Schlegel W, Rodbell M

Abstract

Adenylate cyclase in purified membranes from rat adipocytes is inhibited by low concentrations of purine-modified adenosine analogs, particularly those modified in the N6 position. Such inhibition is antagonized competitively by methylxanthines, but not by other cyclic nucleotide phosphodiesterase inhibitors, and it is dependent on "inhibitory" concentrations of GTP in the assay medium. Ribose-modified adenosine analogs inhibit adenylate cyclase through a process that is neither dependent upon the GTP concentration nor antagonized by methylxanthines. These results explain the potent effects of adenosine and methylxanthines on fat cell metabolism and demonstrate the importance of GTP in mediating inhibition by agents that act at cell surface receptors.

MeSH Terms
Adenosine/analogs & derivatives,pharmacology Adenylyl Cyclase Inhibitors Adipose Tissue/drug effects,enzymology Animals Cell Membrane/enzymology Cyclic AMP/metabolism Guanosine Triphosphate/pharmacology Kinetics Lipid Mobilization/drug effects Xanthines/pharmacology
Chemicals
Adenylyl Cyclase Inhibitors Xanthines methylxanthine Guanosine Triphosphate Cyclic AMP Adenosine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Londos C
Cooper D M
Schlegel W
Rodbell M
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37 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.75.11.5362
Published
1978-11-00
Pages
5362-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC392963
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.75.11.5362 PMC Full Text View journal details
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