| Myocardial beta-adrenoceptor down-regulation by norepinephrine is linked to reduced norepinephrine uptake activity. | |
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MedLine Citation:
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PMID: 10611414 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chronic administration of norepinephrine for 8 weeks has been shown to reduce neuronal norepinephrine uptake activity and increase interstitial norepinephrine concentration in the heart. To determine whether the changes could lead to myocardial beta-adrenoceptor down-regulation or beta-adrenergic subsensitivity, we measured left ventricular contractile responses to dobutamine, myocardial beta-adrenoceptor density, beta subtype distribution, competitive inhibition agonist binding, and adenylyl cyclase activity activation by isoproterenol, 5'-guanylylimidodiphosphate, and forskolin in dogs after a norepinephrine or saline infusion for 8 weeks. We found that norepinephrine infusion reduced myocardial beta-adrenoceptor density, beta(1)-adrenoceptor subtype density, and high-affinity site for isoproterenol. Left ventricular contractile responses to dobutamine were reduced in the norepinephrine-infused animals. In addition, norepinephrine infusion decreased the basal adenylyl cyclase activity and the adenylyl cyclase responses to isoproterenol, 5'-guanylylimidodiphosphate, and forskolin. The findings indicate that a decrease in cardiac norepinephrine uptake predisposes the heart to norepinephrine-induced myocardial beta-adrenoceptor down-regulation, and that norepinephrine, when present in a sufficient amount over a long period as it is in chronic heart failure, can reduce myocardial beta-adrenergic responsiveness by both homologous and heterologous desensitization. |
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Authors:
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E Dong; A Yatani; A Mohan; C S Liang |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: European journal of pharmacology Volume: 384 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 1999 Nov |
Date Detail:
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Created Date: 2000-01-18 Completed Date: 2000-01-18 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 17-24 Citation Subset: IM |
Affiliation:
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Cardiology Unit, Box 679, Cardiology Research Laboratories, Department of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester NY, USA. |
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 Adrenergic beta-Agonists / pharmacology Adrenergic beta-Antagonists / metabolism, pharmacology Animals Binding, Competitive / drug effects Dobutamine / pharmacology Dogs Down-Regulation / drug effects Enzyme Activation / drug effects Forskolin / pharmacology Guanylyl Imidodiphosphate / pharmacology Heart Ventricles / drug effects*, metabolism Hemodynamics / drug effects Imidazoles / pharmacology Iodine Radioisotopes / diagnostic use Iodocyanopindolol / metabolism, pharmacology Isoproterenol / pharmacology Myocardial Contraction / drug effects Norepinephrine / pharmacokinetics*, pharmacology* Receptors, Adrenergic, beta / drug effects, metabolism* Receptors, Adrenergic, beta-1 / metabolism Receptors, Adrenergic, beta-2 / metabolism Ventricular Function |
| Grant Support | |
ID/Acronym/Agency:
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HL-39260/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Agonists; 0/Adrenergic beta-Antagonists; 0/Imidazoles; 0/Iodine Radioisotopes; 0/Receptors, Adrenergic, beta; 0/Receptors, Adrenergic, beta-1; 0/Receptors, Adrenergic, beta-2; 34273-04-6/Guanylyl Imidodiphosphate; 34368-04-2/Dobutamine; 51-41-2/Norepinephrine; 66428-89-5/Forskolin; 7683-59-2/Isoproterenol; 81015-67-0/CGP 20712A; 83498-72-0/Iodocyanopindolol; EC 4.6.1.1/Adenylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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