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.

β-blockers reverse agonist-induced β2-AR downregulation regardless of their signaling profile / Maccari, S.; Vezzi, V.; Barbagallo, F.; Stati, T.; Ascione, B.; Gro, M. C.; Catalano, L.; Marano, G.; Matarrese, P.; Ambrosio, C.; Molinari, P.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 21:2(2020). [10.3390/ijms21020512]

β-blockers reverse agonist-induced β2-AR downregulation regardless of their signaling profile

Barbagallo F.
Membro del Collaboration Group
;
2020

Abstract

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.
2020
cell surface receptor density; cultured cells; lymphocytes; pharmacology; β-blockers
01 Pubblicazione su rivista::01a Articolo in rivista
β-blockers reverse agonist-induced β2-AR downregulation regardless of their signaling profile / Maccari, S.; Vezzi, V.; Barbagallo, F.; Stati, T.; Ascione, B.; Gro, M. C.; Catalano, L.; Marano, G.; Matarrese, P.; Ambrosio, C.; Molinari, P.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 21:2(2020). [10.3390/ijms21020512]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1361242
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