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Open AccessArticle

β-blockers Reverse Agonist-Induced β2-AR Downregulation Regardless of Their Signaling Profile

1
Center for Gender-Specific Medicine, National Institute of Health, 00161 Rome, Italy
2
National Center for Drug Research and Evaluation, National Institute of Health, 00161 Rome, Italy
3
Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy
4
National Blood Center, 00161 Rome, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Ambrosio and Molinari should be considered as senior authors.
Int. J. Mol. Sci. 2020, 21(2), 512; https://doi.org/10.3390/ijms21020512
Received: 25 November 2019 / Revised: 30 December 2019 / Accepted: 10 January 2020 / Published: 14 January 2020
(This article belongs to the Section Molecular Pharmacology)
Altered β-adrenergic receptor (β-AR) density has been reported in cells, animals, and humans receiving β-blocker treatment. In some cases, β-AR density is upregulated, but in others, it is unaffected or even reduced. Collectively, these results would imply that changes in β-AR density and β-blockade are not related. However, it has still not been clarified whether the effects of β-blockers on receptor density are related to their ability to activate different β-AR signaling pathways. To this aim, five clinically relevant β-blockers endowed with inverse, partial or biased agonism at the β2-AR were evaluated for their effects on β2-AR density in both human embryonic kidney 293 (HEK293) cells expressing exogenous FLAG-tagged human β2-ARs and human lymphocytes expressing endogenous β2-ARs. Cell surface β2-AR density was measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Treatment with propranolol, carvedilol, pindolol, sotalol, or timolol did not induce any significant change in surface β2-AR density in both HEK293 cells and human lymphocytes. On the contrary, treatment with the β-AR agonist isoproterenol reduced the number of cell surface β2-ARs in the tested cell types without affecting β2-AR-mRNA levels. Isoproterenol-induced effects on receptor density were completely antagonized by β-blocker treatment. In conclusion, the agonistic activity of β-blockers does not exert an important effect on short-term regulation of β2-AR density. View Full-Text
Keywords: pharmacology; cell surface receptor density; β-blockers; cultured cells; lymphocytes pharmacology; cell surface receptor density; β-blockers; cultured cells; lymphocytes
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Maccari, S.; Vezzi, V.; Barbagallo, F.; Stati, T.; Ascione, B.; Grò, M.C.; Catalano, L.; Marano, G.; Matarrese, P.; Ambrosio, C.; Molinari, P. β-blockers Reverse Agonist-Induced β2-AR Downregulation Regardless of Their Signaling Profile. Int. J. Mol. Sci. 2020, 21, 512.

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