Document Detail


Beta-adrenergic receptor desensitization of wild-type but not cyc lymphoma cells unmasked by submillimolar Mg2+.
MedLine Citation:
PMID:  2820824     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Treatment with low physiological concentrations of epinephrine (5-50 nM) rapidly desensitizes beta-adrenergic stimulation of cAMP formation in S49 wild-type (WT) lymphoma cells. Previous attempts to detect this early phase of desensitization in cell-free assays of adenylate cyclase (EC 4.6.1.1) after intact cell treatment were unsuccessful. We have now found that reducing the Mg2+ concentrations in the adenylate cyclase assays to less than 1.0 mM unmasked this rapid phase of desensitization of the WT cells, and that high Mg2+ concentrations (5-10 mM) largely obscured the desensitization. Submillimolar Mg2+ conditions also revealed a two- to threefold decrease in the affinity of epinephrine binding to the beta-adrenergic receptor after desensitization with 20 nM epinephrine. Detection of 4 beta-phorbol 12-myristate 13-acetate (PMA) desensitization of the WT beta-adrenergic receptor was also dependent on low Mg2+ as measured either by the decrease in epinephrine stimulation of adenylate cyclase or by the reduction in the affinity of epinephrine binding. Unexpectedly, when cyc- cells were pretreated with 50 nM epinephrine, the beta-adrenergic stimulation of reconstituted adenylate cyclase was not desensitized. The characteristics of the Mg2+ effect on epinephrine- and PMA-induced desensitizations suggest a similar mechanism of action with the most likely events being phosphorylations of the beta-adrenergic receptors. Our data indicate that cAMP-dependent protein kinase (EC 2.7.1.37) may play a role in the desensitization caused by low epinephrine concentrations inasmuch as this phase of desensitization did not occur in the cyc-. For the PMA-induced desensitization, the phosphorylation may be mediated by protein kinase C (EC 2.7.1.37).
Authors:
R B Clark; J Friedman; J A Johnson; M W Kunkel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  1     ISSN:  0892-6638     ISO Abbreviation:  FASEB J.     Publication Date:  1987 Oct 
Date Detail:
Created Date:  1987-11-16     Completed Date:  1987-11-16     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  289-97     Citation Subset:  IM    
Affiliation:
Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston 77225.
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / metabolism
Animals
Cell Line
Epinephrine / pharmacology
Lymphoma / metabolism
Magnesium / physiology*
Receptors, Adrenergic, beta / drug effects,  metabolism,  physiology*
Subcellular Fractions / metabolism
Tetradecanoylphorbol Acetate / pharmacology
Tumor Cells, Cultured / metabolism
Chemical
Reg. No./Substance:
0/Receptors, Adrenergic, beta; 16561-29-8/Tetradecanoylphorbol Acetate; 51-43-4/Epinephrine; 7439-95-4/Magnesium; EC 4.6.1.1/Adenylate Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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