Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
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.
DEVREOTES, P.N., GARDNER, J.M. & FAMBROUGH, D.M. (1977). Kinetics of biosynthesis of the acetylcholine receptor and its subsequent incorporation into the plasma membrane of cultured chick skeletal muscle. Cell, 10, 365–373.
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).
DOSS, R.C., PERKINS, J.P. & HARDEN, T.K. (1981). Recovery of β-adrenergic receptors following long-term exposure of astrocytoma cells to catecholamine: role of protein synthesis. J. biol. Chem., 256, 12281–12286.
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.
HARDEN, T.K. (1983). Agonist-induced desensitization of the β-adrenergic receptor-linked adenylate cyclase. Pharmac. Rev., 35, 5–32.
HARDEN, T.K., COTTON, C.U., WALDO, G.L., LUTTON, J.K. & PERKINS, J.P. (1980). Catecholamine-induced alteration in the sedimentation behaviour of membrane bound β-adrenergic receptors. Science, 210, 441–443.
HARDEN, T.K., FOSTER, S.J. & PERKINS, J.P. (1979). Differential expression of the components of the adenylate system during growth of astrocytoma cells in culture. J. biol. Chem., 254, 4416–4422.
HELENIUS, A., MELLMAN, I., WALL, D. & HUBBARD, A. (1983). Endosomes. TIBS, 6, 245–250.
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).
HERTEL, C. & PERKINS, J.P. Receptor-specific mechanisms of desensitization of β-adrenergic receptor function. Molecular Endocrinology (in press).
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.
HU, A.S.L., BOCK, R.M. & HALVORSON, H.O. (1962). Separation of labelled from unlabelled proteins by equilibrium density gradient sedimentation. Analyt. Biochem., 4, 489–504.
LEFKOWITZ, R.J., WESSELS, M.R. & STADEL, J.M. (1980). Hormones, receptors, and cyclic AMP: Their role in target cell refractoriness. Current Topics in Cellular Regulation, 17, 205–230.
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.
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.
REED, R.C. & LANE, M.D. (1980). Insulin receptor synthesis and turnover in differentiating 3T3-L1 preadipocytes. Proc. natn. Acad. Sci. U.S.A., 77, 285–289.
STRULOVICI, B., STADEL, J.M. & LEFKOWITZ, R.J. (1983). Functional integrity of desensitized β-adrenergic receptors. Internalized receptors reconstitute catecholamine-stimulated adenylate cyclase activity. J. biol. Chem., 258, 6410–6414.
SU, Y.-F., HARDEN, T.K. & PERKINS, J.P. (1980). Catecholamine-specific desensitization of adenylate cyclase: Evidence for a multistep process. J. biol. Chem., 255, 7410–7419.
TOEWS, M.L., HARDEN, T.K. & PERKINS, J.P. (1983). High affinity binding of agonists to β-adrenergic receptors on intact cells. Proc. natn. Acad. Sci. U.S.A., 80, 3553–3557.
TOEWS, M.L. & PERKINS, J.P. (1984). Agonist-induced changes in β-adrenergic receptors on intact cells. J. biol. Chem., 259, 2227–2235.
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).
WALDO, G., NORTHUP, J.K., PERKINS, J.P. & HARDEN, T.K. (1983). Characterization of an altered membrane form of the β-adrenergic receptor produced during agonist-induced desensitization. J. biol. Chem., 258, 13900–13908.
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).
Author information
Authors and Affiliations
Editor information
Copyright information
© 1984 Macmillan Publishers Limited
About this chapter
Cite this chapter
Perkins, J.P., Harden, T.K. (1984). Mechanisms of desensitization of β-adrenergic receptors. In: Paton, W., Mitchell, J., Turner, P. (eds) IUPHAR 9th International Congress of Pharmacology London 1984. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-17613-7_8
Download citation
DOI: https://doi.org/10.1007/978-1-349-17613-7_8
Publisher Name: Palgrave Macmillan, London
Print ISBN: 978-0-333-37134-3
Online ISBN: 978-1-349-17613-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)