| Beta-adrenergic receptor desensitization of wild-type but not cyc lymphoma cells unmasked by submillimolar Mg2+. | |
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MedLine Citation:
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PMID: 2820824 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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). |
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Authors:
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R B Clark; J Friedman; J A Johnson; M W Kunkel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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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:
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Created Date: 1987-11-16 Completed Date: 1987-11-16 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 289-97 Citation Subset: IM |
Affiliation:
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Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston 77225. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenylate Cyclase
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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:
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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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