Abstract
Desensitization, the tendency of biological responses to wane over time despite the continuous presence of a stimulus of constant intensity, is observed in organisms as diverse as bacteria and mammals. Recently, new insights into the molecular mechanisms underlying these phenomena have emerged from the study of the receptors coupled to the ubiquitous second messenger-generating system adenylate cyclase. These mechanisms involve sequestration or down-regulation of the receptors from the cell surface as well as functionally significant covalent modifications of the receptors and / or guanine nucleotide regulatory proteins.
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References
Lefkowitz, R. J., Wessels, M. R. & Stadel, J. M. Curr. Top. Cell. Regul. 17, 205–230 (1980).
Perkins, J. P. Curr. Top. Membranes Transp. 18, 85–108 (1983).
Harden, T. K. Pharmac. Rev. 35, 5–32 (1983).
Hertel, C. & Perkins, J. P. Molec. cell. Endocr. 37, 245–256 (1984).
Benovic, J. L., Shorr, R. G. L., Caron, M. G. & Lefkowitz, R. J. Biochemistry 23, 4510–4518 (1984).
Cubero, A. & Malbon, C. C. J. biol. Chem. 259, 1344–1350 (1984).
Shorr, R. G. L., Lefkowitz, R. J. & Caron, M. G. J. biol. Chem. 256, 5820–5826 (1981).
Shorr, R. G. L., Strohsacker, M. W., Lavin, T. N., Lefkowitz, R. J. & Caron, M. G. J. biol. Chem. 257, 12341–12350 (1982).
Sibley, D. R., Peters, J. R., Nambi, P., Caron, M. G. & Lefkowitz, R. J. Biochem. biophys. Res. Commun. 119, 458–464 (1984).
Codina, J. et al. Adv. Cyclic Nucleotide Res. 17, 111–126 (1984).
Gilman, A. G. Cell 36, 577–579 (1984).
Pfeuffer, E., Dreher, R. M., Metzger, H. & Pfeuffer, T. Proc. natn. Acad. Sci. U.S.A. 82, 3086–3090 (1985).
Stadel, J. M. & Lefkowitz, R. J. Curr. Top. Membranes Transp. 18, 45–66 (1983).
Schramm, M. & Selinger, Z. Science 225, 1350–1356 (1984).
Mukherjee, C., Caron, M. G. & Lefkowitz, R. J. Proc. natn. Acad. Sci. U.S.A. 72, 1945–1949 (1975).
Mukherjee, C., Caron, M. G. & Lefkowitz, R. J. Endocrinology 99, 347–357 (1976).
Mickey, J., Tate, R. & Lefkowitz, R. J. J. biol. Chem. 250, 5727–5729 (1975).
Mickey, J. V., Tate, T., Mullikin, D. & Lefkowitz, R. J. Molec. Pharmac. 12, 409–419 (1976).
Wessels, M. R., Mullikin, D. & Lefkowitz, R. J. J. biol. Chem. 253, 3371–3373 (1978).
Wessels, M. R., Mullikin, D. & Lefkowitz, R. J. Molec. Pharmac. 16, 10–20 (1979).
Shear, M., Insel, P. A., Melmon, K. L. & Coffino, P. J. biol. Chem. 251, 7572–7576 (1976).
Su, Y.-F., Harden, T. K. & Perkins, J. P. J. biol. Chem. 254, 38–41 (1979).
Harden, T. K., Su, Y.-F. & Perkins, J. P. J. Cyclic Nucleotide Res. 5, 99–106 (1979).
Su, Y.-F., Harden, T. K. & Perkins, J. P. J. biol. Chem. 255, 7410–7419 (1980).
Homburger, V. et al. J. biol. Chem. 255, 10436–10444 (1980).
Fishman, P. H., Mallorga, P. & Tallman, J. F. Molec. Pharmac. 20, 310–318 (1981).
Green, D. A. & Clark, R. B. J. biol. Chem. 256, 2105–2108 (1981).
Green, D. A., Friedman, J. & Clark, R. B. J. Cyclic Nucleotide Res. 7, 161–172 (1981).
Iyengar, R., Bhat, M. K., Riser, M. E. & Birnbaumer, L. J. biol. Chem. 256, 4810–4815 (1981).
Chuang, D.-M. & Costa, E. Proc. natn. Acad. Sci. U.S.A. 76, 3024–3028 (1979).
Chuang, D.-M., Kinnier, W. J., Farber, L. & Costa, E. Molec. Pharmac. 18, 348–355 (1980).
Chuang, D.-M. & Costa, E. Neurochem. Res. 4, 777–793 (1979).
Stadel, J. M. et al. J. biol. Chem. 258, 3032–3038 (1983).
Strasser, R. H., Stiles, G. L. & Lefkowitz, R. J. Endocrinology 115, 1392–1400 (1984).
Harden, T. K., Cotton, C. U., Waldo, G. L., Lutton, J. K. & Perkins, J. P. Science 210, 441–443 (1980).
Waldo, G. L., Northup, J. K., Perkins, J. P. & Harden, T. K. J. biol. Chem. 258, 13900–13908 (1983).
Toews, M. L., Waldo, G. L., Harden, T. K. & Perkins, J. P. J. biol. Chem. 259, 11844–11850 (1984).
Frederich, R. C. Jr, Waldo, G. L., Harden, T. K. & Perkins, J. P. J. Cyclic Nucleotide Prot. Phosphor. Res. 9, 103–118 (1983).
Hertel, C., Staehelin, M. & Perkins, J. P. J. Cyclic Nucleotide Prot. Phosphor. Res. 9, 119–128 (1983).
Hertel, C., Muller, P., Portenier, M. & Staehelin, M. Biochem. J. 216, 669–674 (1983).
Staehelin, M., Simons, P., Jaegg, K. & Wigger, N. J. biol. Chem. 258, 3496–3502 (1983).
Staehelin, M. & Hertel, C. J. receptor Res. 3, 35–43 (1983).
Pittman, R. N. & Molinoff, P. B. J. Cyclic Nucleotide Res. 6, 421–435 (1980).
Pittman, R. N. & Molinoff, P. B. Molec. Pharmac. 24, 398–408 (1983).
Toews, M. L., Harden, T. K. & Perkins, J. P. Proc. natn. Acad. Sci. U.S.A. 80, 3553–3557 (1983).
Toews, M. L. & Perkins, J. P. J. biol. Chem. 259, 2227–2235 (1984).
Insel, P. A., Mahan, L. C., Motulsky, H. J., Stoolman, L. M. & Koachman, A. M. J. biol. Chem. 258, 13597–13605 (1983).
Hoyer, D., Reynolds, E. E. & Molinoff, P. B. Molec. Pharmac. 25, 209–218 (1984).
Morishima, I., Thompson, W. J., Robison, G. A. & Strada, S. J. Molec. Pharmac. 18, 370–378 (1980).
Doss, R. C., Perkins, J. P. & Harden, T. K. J. biol. Chem. 256, 12281–12286 (1981).
Su, Y.-F., Cubeddu, L. X. & Perkins, J. P. J. Cyclic Nucleotide Res. 2, 257–270 (1976).
Mahan, L. C., Koachman, A. M. & Insel, P. A. Proc. natn. Acad. Sci. U.S.A. 82, 129–133 (1985).
Strulovici, B., Stadel, J. M. & Lefkowitz, R. J. J. biol. Chem. 258, 6410–6414 (1983).
Clark, R. B., Friedman, J., Prashad, N. & Ruoho, A. E. J. Cyclic Nucleotide Prot. Phosphor. Res. 10, 97–119 (1985).
Strasser, R. H. & Lefkowitz, R. J. J. biol. Chem. 260, 4561–4564 (1985).
Kassis, S. & Fishman, P. H. Proc. natn. Acad. Sci. U.S.A. 81, 6686–6690 (1984).
Anderson, W. B. & Jaworski, C. J. J. biol. Chem. 254, 4596–4601 (1979).
Salomon, Y., Ezra, E. & Amir-Zaltsman, Y. Adv. Cyclic Nucleotide Res. 14, 101–109 (1981).
Hunzicker-Dunn, M., Derda, D., Jungmann, R. A. & Birnbaumer, L. Endocrinology 104, 1785–1793 (1979).
Sibley, D. R., Strasser, R. H., Caron, M. G. & Lefkowitz, R. J. J. biol. Chem. 260, 3883–3886 (1985).
Pastan, I. H. & Willingham, M. C. A. Rev. Physiol. 43, 239–250 (1981).
Strader, C. D., Sibley, D. R. & Lefkowitz, R. J. Life Sci. 35, 1601–1610 (1984).
Johnson, G. L., Wolfe, B. B., Harden, T. K., Molinoff, P. B. & Perkins, J. P. J. biol. Chem. 253, 1472–1480 (1978).
de Vellis, J. & Brooker, G. Science 186, 1221–1223 (1974).
Terasaki, W. L. et al. Adv. Cyclic Nucleotide Res. 9, 33–52 (1978).
Nichols, G. A. & Brooker, G. J. Cyclic Nucleotide Res. 5, 435–447 (1979).
Nichols, G. A. & Brooker, G. J. biol. Chem. 255, 23–26 (1980).
Barovsky, K., Pedone, C. & Brooker, G. J. Cyclic Nucleotide Prot. Phosphor. Res. 9, 181–189 (1983).
Kassis, S. & Fishman, P. H. J. biol. Chem. 257, 5312–5318 (1982).
Garrity, M. J., Andreasen, T. J., Storm, D. R. & Robertson, R. P. J. biol. Chem. 258, 8692–8697 (1983).
Kirchik, H. J., Iyengar, R. & Birnbaumer, L. Endocrinology 113, 1638–1646 (1983).
Rich, K. A. et al. J. biol. Chem. 259, 7893–7901 (1984).
Hoffman, B. B., Mullikin-Kilpatrick, D. & Lefkowitz, R. J. J. Cyclic Nucleotide Res. 5, 355–366 (1979).
Simpson, I. A. & Pfeuffer, T. Eur. J. Biochem. 111, 111–116 (1980).
Hudson, T. H. & Johnson, G. L. Molec. Pharmac. 20, 694–703 (1981).
Briggs, M. M., Stadel, J. M., Iyengar, R. & Lefkowitz, R. J. Archs Biochem. Biophys. 224, 142–151 (1983).
Stadel, J. M. et al. J. biol. Chem. 257, 9242–9245 (1982).
Strulovici, B., Cerione, R. A., Kilpatrick, B. F., Caron, M. G. & Lefkowitz, R. J. Science 225, 837–840 (1984).
Stadel, J. M. et al. Proc. natn. Acad. Sci. U.S.A. 80, 3173–3177 (1983).
Sibley, D. R., Peters, J. R., Nambi, P., Caron, M. G. & Lefkowitz, R. J. J. biol. Chem. 259, 9742–9749 (1984).
Nambi, P. et al. J. biol. Chem. 259, 4629–4633 (1984).
Nambi, P., Peters, J. R., Sibley, D. R. & Lefkowitz, R. J. J. biol. Chem. 260, 2165–2171 (1985).
Benovic, J. L. et al. J. biol. Chem. 260, 7094–7101 (1985).
Sibley, D. R., Nambi, P., Peters, J. R. & Lefkowitz, R. J. Biochem. biophys. Res. Commun. 121, 973–979 (1984).
Kelleher, D. J., Pessin, J. E., Ruoho, A. E. & Johnson, G. L. Proc. natn. Acad. Sci. U.S.A. 81, 4316–4320 (1984).
Stadel, J. M., De Lean, A., Mullikin-Kilpatrick, D., Sawyer, D. D. & Lefkowitz, R. J. J. Cyclic Nucleotide Res. 7, 37–47 (1981).
Noda, C. et al. J. biol. Chem. 259, 7747–7754 (1984).
Koschel, K. Eur. J. Biochem. 108, 163–169 (1980).
Attramadal, H., Le Gac, F., Jahnsen, T. & Hansson, V. Molec. cell. Endocr. 34, 1–6 (1984).
Leeb-Lundberg, L. M. F. et al. Proc. natn. Acad. Sci. U.S.A. (in the press).
Liebman, P. A. & Sitaramayya, A. Adv. Cyclic Nucleotide Prot. Phosphor. Res. 17, 215–225 (1984).
Shichi, H. & Somers, R. L. J. biol. Chem. 253, 7040–7046 (1978).
Somers, R. L. & Klein, D. C. Science 226, 182–184 (1984).
Shichi, H., Yamamoto, K. & Somers, R. L. Vision Res. (in the press).
Engstrom, P. & Hazelbauer, G. L. Cell 20, 165–171 (1980).
De Franco, A. L. & Koshland, D. E. Jr Proc. natn. Acad. Sci. U.S.A. 77, 2429–2434 (1980).
Goy, M. F., Springer, M. S. & Adler, J. Proc. natn. Acad. Sci. U.S.A. 74, 4964–4969 (1977).
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Sibley, D., Lefkowitz, R. Molecular mechanisms of receptor desensitization using the β-adrenergic receptor-coupled adenylate cyclase system as a model. Nature 317, 124–129 (1985). https://doi.org/10.1038/317124a0
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DOI: https://doi.org/10.1038/317124a0
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