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Downregulation of beta-adrenergic receptors by low density lipoproteins and its prevention by beta-adrenergic receptor antagonists. 1998

B R Brehm, and M Meergans, and D I Axel, and M Pfohl, and H Heinle, and K R Karsch
Department of Cardiology, University of Tübingen, Germany. 101566.341@compuserve.com

OBJECTIVE 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. RESULTS 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, P < 0.01). 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D008077 Lipoproteins, LDL A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
D008297 Male Males
D008790 Metoprolol A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS. Beloc-Duriles,Betaloc,Betaloc-Astra,Betalok,CGP-2175,H 93-26,Lopressor,Metoprolol CR-XL,Metoprolol Succinate,Metoprolol Tartrate,Seloken,Spesicor,Spesikor,Toprol,Toprol-XL,Beloc Duriles,Betaloc Astra,CGP 2175,CGP2175,H 93 26,H 9326,Metoprolol CR XL,Toprol XL
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D011412 Propanolamines AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives. Aminopropanols
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D003331 Coronary Vessels The veins and arteries of the HEART. Coronary Arteries,Sinus Node Artery,Coronary Veins,Arteries, Coronary,Arteries, Sinus Node,Artery, Coronary,Artery, Sinus Node,Coronary Artery,Coronary Vein,Coronary Vessel,Sinus Node Arteries,Vein, Coronary,Veins, Coronary,Vessel, Coronary,Vessels, Coronary
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D000262 Adenylyl Cyclases Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP. Adenyl Cyclase,Adenylate Cyclase,3',5'-cyclic AMP Synthetase,Adenylyl Cyclase,3',5' cyclic AMP Synthetase,AMP Synthetase, 3',5'-cyclic,Cyclase, Adenyl,Cyclase, Adenylate,Cyclase, Adenylyl,Cyclases, Adenylyl,Synthetase, 3',5'-cyclic AMP

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