Certain beta-blockers can decrease beta-adrenergic receptor number: II. Down-regulation of receptor number by alprenolol and propranolol in cultured lymphoma and muscle cells.

Hughes, Richard J.; Mahan, Lawrence C.; Insel, Paul A.

doi:10.1161/01.res.63.2.279

Cited by 18 publications

(4 citation statements)

References 22 publications

(10 reference statements)

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“…Aarons and Molinoff [7] reported that the influence of a β-antagonist is able to increase the β-AR number in heart, lung and lymphocytes of rats after 7 days of treatment. In contrast to this observation, in membranes prepared from BC3H-1 muscle cells and in intact S49 mouse lymphoma cells, which both contain a pure population of β # -receptors, propranolol failed to increase the receptor number and elicited a substantial 20-70 % decrease in receptor number after 16-20 h of treatment [28]. In our studies, H9c2 (2-1) cells were incubated with propranolol for 24 h without any changes in either the total β-receptor level or in the β # -mRNA level.…”

Section: Discussioncontrasting

confidence: 68%

Regulation of β-adrenoceptor density and mRNA levels in the rat heart cell-line H9c2

Dangel

Giray

Ratge

et al. 1996

Biochemical Journal

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The regulation of the expression of beta-adrenoceptor (beta-ARs) is not thoroughly understood. We demonstrate that the rat heart cell-line H9c2 expresses both beta 1- and beta 2-ARs. In radioligand-binding experiments, the maximal binding capacity of (-)-[125I]-iodocyanopindolol was determined as 18 +/- 0.6 fmol/mg of protein with a KD of 35.4 +/- 4.1 pM. Competitive radioligand-binding experiments with subtype-specific beta-antagonists reveal a subtype ratio of beta 1- to beta 2-ARs of 29%: 71%. With competitive reverse-transcriptase PCR we found beta 2-mRNA to be up to 1600 times more frequent than beta 1-mRNA. Treatment of the H9c2 cell-line with the beta-adrenergic agonist (-)-isoproterenol (10(-6) M), the antagonist (-)-propranolol (10(-6) M) and the glucocorticoid dexamethasone (500 nM) induces regulatory effects on both the beta-AR protein and mRNA level. Isoproterenol treatment leads to down-regulation of the total receptor number by 56 +/- 4%, due to a decrease in beta 2-ARs, while maintaining the beta 1-AR number constant. On the transcription level, both beta 1-and beta 2-mRNAs are decreased by 30% and 42% respectively. mRNA stability measurements reveal a reduced half-life of beta 2-mRNA from 9.3 h to 6.5 h after isoproterenol treatment. Incubation of cells with (-)-propranolol does not affect the amounts of beta-ARs and their mRNAs. Dexamethasone induces a 1.8 +/- 0.2-fold increase in beta-AR number over the basal level as well as a 1.9 +/- 0.2-fold increase in the amount of beta 2-mRNA. Because the half-life of beta 2-mRNA was unaffected by dexamethasone, the increased beta 2-mRNA level must be due to an enhanced transcription rate. The beta 1-mRNA levels are unchanged during dexamethasone-incubation of the cells. Our data clearly demonstrate that treatment of H9c2 rat heart cells with isoproterenol and dexamethasone induces alterations in the level of RNA stability as well as gene transcription, leading to altered receptor numbers.

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Section: Discussioncontrasting

confidence: 68%

Regulation of β-adrenoceptor density and mRNA levels in the rat heart cell-line H9c2

Dangel

Giray

Ratge

et al. 1996

Biochemical Journal

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“…However, the eect of drug treatment on receptor density appeared dierent in other studies with dierent experimental settings. For example, Hughes et al (1988) reported downregulation of b-AR by propranolol in cultured lymphoma and muscle cells. Extrapolation of observations from such studies to the clinic is dicult and should be done with great care.…”

Section: Eects Of Long-term Treatment With Inverse Agonistsmentioning

confidence: 99%

“…However, the effect of drug treatment on receptor density appeared different in other studies with different experimental settings. For example, Hughes et al . (1988) reported downregulation of β‐AR by propranolol in cultured lymphoma and muscle cells.…”

Section: Introductionmentioning

confidence: 99%

Inverse agonism at G protein‐coupled receptors: (patho)physiological relevance and implications for drug discovery

Ligt

Kourounakis

IJzerman

2000

British J Pharmacology

169

108

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“…We have not determined if the initial diminution of DHAP binding at low propranolol concentrations seen in Figure 4 represents the actual removal of binding sites from the cell surface or the prolonged occupancy of surface receptors by the antagonist. The alteration of receptor numbers in response to receptor occupancy is commonly encountered and is a crucial element in how a cell reacts to and interprets relevant stimuli (19)(20)(21)(22)(23). Both agonists and antagonists of receptor function are capable of eliciting these responses.…”

Section: Regulation Of Binding Site Number By B-blockage and Dexawethmentioning

confidence: 99%

Regulation of Lens β-Adrenergic Receptors by Receptor Occupancy and Dexamethasone

Ireland

Richiert

Tran

1994

Journal of Ocular Pharmacology and Therapeutics

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ß-adrenergic binding sites in primary cultures of chick lens annular pad (CLAP) cells were characterized with dihydroalprenolol (DHAP). Binding site affinities and densities were similar to ß-adrenergic receptors (ßARs) previously characterized on crude membranes from freshly isolated cells. In competitive displacement studies, the ß-blocker propranolol was shown to increase the number of available binding sites in a concentration dependent manner. Acute exposure of CLAP cells to propranolol prior to DHAP binding also resulted in an increase in the number of available binding sites. Finally, lens ß-adrenergic binding site levels could be modulated by dexamethasone treatment. These results indicate that lens ßARs are subject to common regulatory mechanisms and further implicate ophthalmic pharmaceuticals as possible cataractogenic agents.

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Certain beta-blockers can decrease beta-adrenergic receptor number: II. Down-regulation of receptor number by alprenolol and propranolol in cultured lymphoma and muscle cells.

Cited by 18 publications

References 22 publications

Regulation of β-adrenoceptor density and mRNA levels in the rat heart cell-line H9c2

Regulation of β-adrenoceptor density and mRNA levels in the rat heart cell-line H9c2

Inverse agonism at G protein‐coupled receptors: (patho)physiological relevance and implications for drug discovery

Regulation of Lens β-Adrenergic Receptors by Receptor Occupancy and Dexamethasone

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