Downregulation of beta-adrenergic receptors by low density lipoproteins and its prevention by beta-adrenergic receptor antagonists
| Autor: | Dorothea I. Axel, M. Pfohl, Helmut Heinle, Matthias Meergans, Karl R. Karsch, Bernhard R. Brehm |
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| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Adrenergic receptor Physiology Swine Adrenergic beta-Antagonists Iodocyanopindolol Down-Regulation Vasodilation In Vitro Techniques Muscle Smooth Vascular Adenylyl cyclase Propanolamines chemistry.chemical_compound Downregulation and upregulation Physiology (medical) Internal medicine medicine Radioligand Animals Bisoprolol Receptor Metoprolol Dose-Response Relationship Drug Chemistry Cell Membrane Coronary Vessels Lipoproteins LDL Endocrinology Female Cardiology and Cardiovascular Medicine medicine.drug Adenylyl Cyclases |
| Zdroj: | Cardiovascular research. 38(2) |
| ISSN: | 0008-6363 |
| Popis: | Vasodilation by beta-adrenergic receptors of smooth muscle cells appears to be impaired early after the onset of hypercholesteremia. The aim of this study was to analyze the modulation of beta-adrenergic receptor density and adenylyl cyclase activity in the presence of moderately elevated concentrations of LDL. The effects of beta 1- and beta 2-adrenergic receptor antagonists on LDL-induced receptor changes were studied.Media explants of porcine coronary arteries were incubated with moderately elevated LDL concentrations (0.7-3.9 mmol/l). The density of beta-adrenergic receptors was determined in plasma membranes using the radioligand [125I]iodocyanopinodolol. LDL (3.9 mmol/l) resulted in a decrease of beta-adrenergic receptor density (control 137 +/- 5 vs. 89 +/- 7 fmol/mg protein, P0.01). After removal of LDL and cultivation for an additional 3 days beta-adrenergic receptors increased to 129 +/- 5 fmol/mg. In the presence of the beta 1- or beta 2-adrenergic receptor antagonists the LDL-mediated decrease was inhibited. Addition of metoprolol after 3 days of LDL incubation caused a restoration of receptor density. The basal, isoproterenol- and forskolin-stimulated adenylyl cyclase activities were increased after LDL incubation by 180, 110 or 80%, respectively.Moderately elevated LDL levels decreased beta-adrenergic receptor density while adenylyl cyclase activity was simultaneously increased. beta 1- or beta 2-adrenergic receptor antagonists prevented this receptor decrease and might preserve the beta-adrenergic receptor density in the presence of moderately elevated LDL levels. |
| Databáze: | OpenAIRE |
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