Mechanisms of desensitization of β-adrenergic receptors
For the past several years we and our colleagues have been involved in a study of catecholamine-induced desensitization of the β-adrenergic receptor (βAR)-linked adenylate cyclase system. There appears to be a number of processes utilized by cells to reduce responsiveness to catecholamines (see Lefkowitz et al., 1980; Perkins et al., 1982; Harden, 1983; Hertel & Perkins, 1985 for recent reviews). Our studies have focused on a desensitization process that is βAR-specific, that is, it results in changes in the system that eliminate responsiveness only to catecholamines.
KeywordsAdenylate Cyclase Adrenergic Receptor Adenylate Cyclase Activity Adenylate Cyclase System Frog Erythrocyte
Unable to display preview. Download preview PDF.
- BENOVIC, J.L., CERIONE, R.A., CODINA, J., BIRNBAUMER, L., LEFKOWITZ, R.J. & CARON, M.G. (1984). Deglycosylation of the pure β-adrenergic receptor. Fedn Proc., 43, 1578. Abst. 949.Google Scholar
- DOSS, R.C., KRAMARCY, N.R., HARDEN, T.K. & PER-KINS, J.P. (1985). Effects of tunicamycin on the β-adrenergic receptor during cell growth and during recovery from agonist-induced down regulation. Mol. Pharmac. (in press).Google Scholar
- FREDERICH, R., WALDO, G., HARDEN, T.K. & PERKINS, J.P. (1983). Characterization of agonist-induced β-adrenergic receptor-specific desensitization in C62B glioma cells. J. Cyclic Nuc. Res., 9, 103–118.Google Scholar
- HARDEN, T.K. (1983). Agonist-induced desensitization of the β-adrenergic receptor-linked adenylate cyclase. Pharmac. Rev., 35, 5–32.Google Scholar
- HELENIUS, A., MELLMAN, I., WALL, D. & HUBBARD, A. (1983). Endosomes. TIBS, 6, 245–250.Google Scholar
- HERTEL, C., AFFOLTER, H., PORTENIER, M. & STAEHELIN, M. (1984). Desensitized β-adrenoceptors of C6-glioma cells have distinct binding properties. Naunyn Schmiedeberg’s Arch. Pharmac. (in press).Google Scholar
- HERTEL, C. & PERKINS, J.P. Receptor-specific mechanisms of desensitization of β-adrenergic receptor function. Molecular Endocrinology (in press).Google Scholar
- HERTEL, C., STAEHELIN, M. & PERKINS, J.P. (1983). Evidence for intravesicular β-adrenergic receptors in membrane fractions from desensitized cells: binding of the hydropholic ligand CGP-12177 only in the presence of Alamethicin. J. Cyclic. Nuc. Res., 9, 119–128.Google Scholar
- PERKINS, J.P., HARDEN, T.K. & HARPER, J. (1981). Acute and Chronic Modulation of the Responsiveness of Receptor-Associated Adenylate Cyclase. In Handbook of Experimental Pharmacology. Nathanson, J.A. & Kebabian, J. (eds), Springer-Verlag.Google Scholar
- PITTMANN, R.N. & MOLINOFF, P.B. (1980). Interactions of agonists and antagonists with β-adrenergic receptors on intact L6 muscle cells. J. Cyclic Nuc. Res., 6, 421–435.Google Scholar
- TOEWS, M.L., HARDEN, T.K. & PERKINS, J.P. (1984). Relation between agonist-induced, low affinity β-adrenergic receptors and an agonist-induced, low density vesicular form of the receptor. J. biol. Chem. (in press).Google Scholar
- WALDO, G.L., DOSS, R.C., PERKINS, J.P. & HARDEN, T.K. (1985). Use of a density-shift method to assess -adrenergic receptor synthesis during recovery from catecholamine-induced down-regulation. Mol. Pharmac. (in press).Google Scholar