Altered &beta
adrenergic receptor (&beta
AR) density has been reported in cells, animals, and humans receiving &beta
blocker treatment. In some cases, &beta
AR density is upregulated, but in others, it is unaffected or even reduced. Collectively, these results would imply that changes in &beta
AR density and &beta
blockade are not related. However, it has still not been clarified whether the effects of &beta
blockers on receptor density are related to their ability to activate different &beta
AR signaling pathways. To this aim, five clinically relevant &beta
blockers endowed with inverse, partial or biased agonism at the &beta
2-AR were evaluated for their effects on &beta
2-AR density in both human embryonic kidney 293 (HEK293) cells expressing exogenous FLAG-tagged human &beta
2-ARs and human lymphocytes expressing endogenous &beta
2-ARs. Cell surface &beta
2-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 &beta
2-AR density in both HEK293 cells and human lymphocytes. On the contrary, treatment with the &beta
AR agonist isoproterenol reduced the number of cell surface &beta
2-ARs in the tested cell types without affecting &beta
2-AR-mRNA levels. Isoproterenol-induced effects on receptor density were completely antagonized by &beta
blocker treatment. In conclusion, the agonistic activity of &beta
blockers does not exert an important effect on short-term regulation of &beta
2-AR density.