β-blockers Reverse Agonist-Induced β
| Autor: | Sonia, Maccari, Vanessa, Vezzi, Federica, Barbagallo, Tonino, Stati, Barbara, Ascione, Maria Cristina, Grò, Liviana, Catalano, Giuseppe, Marano, Paola, Matarrese, Caterina, Ambrosio, Paola, Molinari |
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| Rok vydání: | 2019 |
| Předmět: |
lymphocytes
Cell Membrane Fluorescent Antibody Technique cultured cells Article Cell Line cell surface receptor density Gene Expression Regulation Adrenergic beta-2 Receptor Antagonists Organ Specificity β-blockers Humans Receptors Adrenergic beta-2 pharmacology Adrenergic beta-2 Receptor Agonists Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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