Influence of receptor density on the patterns of beta2-adrenocepter desensitization

European Journal of Pharmacology
G RousseauM Bouvier

Abstract

Sustained stimulation of the beta2-adrenoceptor leads to a desensitization of the receptor-mediated adenylyl cyclase stimulation. While desensitization promoted by nanomolar concentrations of isoproterenol involves the phosphorylation of the beta2-adrenoceptor by protein kinase A alone, both protein kinase A- and beta-adrenoceptor kinase-mediated phosphorylation leading to the binding of beta-arrestin contribute to the desensitization evoked by micromolar concentrations of agonist. In the present study, we assessed the influence of receptor density on the patterns of desensitization induced by these two different levels of stimulation. Murine L cells were transfected with a cDNA encoding the human beta2-adrenoceptor and clonal cell lines expressing various levels of beta2-adrenoceptor were used for the study. In cell lines expressing the highest number of receptor, approx. 150000 sites/cell (approx. 3000 fmol/mg of membrane proteins), pretreatment with micromolar concentrations of isoproterenol causes a desensitization pattern characterized by a reduction in both the potency and the efficacy of isoproterenol to further stimulate the adenylyl cyclase activity. In contrast, desensitization induced by 10 nM isoproterenol resulted ...Continue Reading

References

Jan 1, 1992·Annual Review of Neuroscience·B Kobilka
Jan 1, 1991·Annual Review of Biochemistry·H G DohlmanR J Lefkowitz
Mar 14, 1991·European Journal of Biochemistry·K M TateA D Strosberg
Oct 1, 1987·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R B ClarkM W Kunkel
Jan 1, 1988·Annual Review of Cell Biology·J L BenovicR J Lefkowitz
Aug 1, 1986·Molecular and Cellular Endocrinology·R Barber
Apr 1, 1974·Analytical Biochemistry·Y SalomonM Rodbell
Nov 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·S Kassis, P H Fishman
Sep 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·R Iyengar, L Birnbaumer

❮ Previous
Next ❯

Citations

Jun 30, 2001·European Journal of Pharmacology·G RousseauM Bouvier
Dec 20, 2013·Cell and Tissue Research·Iain R ThompsonRobert C Fowkes
Jul 29, 2000·Canadian Journal of Physiology and Pharmacology·E S Werstiuk, R M Lee
Jul 12, 2007·American Journal of Physiology. Endocrinology and Metabolism·Felice BeitzelGordon S Lynch
Apr 25, 2003·Canadian Journal of Physiology and Pharmacology·Catherine Lavoie, Terence E Hébert
Jan 14, 2003·Biophysical Journal·Peter J Woolf, Jennifer J Linderman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.