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.
Highlights
Catecholamines, acting through α- and β-adrenergic receptors, regulate many physiological functions, such as force and frequency of cardiac contraction, vascular and bronchial tone, and metabolism, and are an essential component of the body’s stress response
Given that the regulation of β-adrenergic receptors (β-AR) expressed by endogenous genes may be more relevant to in vivo receptor regulation, we evaluated the effects of β-blockers on β2-AR density of endogenous β2-ARs expressed in human lymphocytes
Since most studies on the effects of β-blockers on receptor density were performed using the β-blocker propranolol [1,2,3,4,16,17], we evaluated the effects of propranolol on the density of endogenous β2-ARs expressed in HL-1 atrial cardiomyocytes derived from mouse AT-1 cells
Summary
Catecholamines, acting through α- and β-adrenergic receptors, regulate many physiological functions, such as force and frequency of cardiac contraction, vascular and bronchial tone, and metabolism, and are an essential component of the body’s stress response. The tissue responses to catecholamines depend on their relative affinities for receptor adrenergic subtypes, their concentration at the site of the receptor as well as the adrenergic receptor density on target cells Drugs, such as β-blockers, and clinical disorders, such as heart failure, can alter the number of β-adrenergic receptors (β-AR). Treatment with carvedilol, a third-generation β-blocker, was not able to affect myocardial β-AR density in patients with heart failure [5]. Together, these results would imply that changes in receptor density and β-blocking activity of β-blockers are not related. It remains to be ascertained whether β-blocker-induced changes in receptor density are related to other pharmacological properties of β-blockers
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
