Abstract
THE cellular cytoskeleton, composed of microtubules and microfilaments, seems to regulate cell surface receptors for a number of membrane-active agents, including lectins1, immunoglobulins2 and polypeptide hormones3. Patching and capping of membrane receptors is controlled by the activity of microfilaments and microtubules, and, in addition, the cytoskeletal elements may be involved in stabilising the fluidity of the cell surface4,5. Colchicine, an inhibitor of microtubular assembly, and presumably, therefore, of microtubule-associated functions, has been used experimentally to study cellular events thought to be regulated by microtubules5, and clinically in the treatment of gout and other inflammatory disorders6. Evidence from several laboratories indicates that increases in cellular adenosine 3′,5′-monophosphate (cyclic AMP) alter the assembly of micro-tubules7–12. It has been suggested that colchicine augments hormone-stimulated cyclic AMP synthesis in target cells for some13,14, but not all15,18, hormones. To study this latter action of colchicine on a well-defined hormonal system, we have examined the augmentation by colchicine of β-adrenergic amine-stimulated cyclic AMP levels in S49 mouse lymphoma cells, a model system for studying the synthesis of cyclic AMP and the actions of β-adrenergic amines17,18. We report here that colchicine potentiates β-adrenergic-stimulated cyclic AMP accumulation in S49 cells and that this potentiation results from events occurring beyond the interaction of β-adrenergic agonists with β-adrenoreceptors.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ukena, T. E., Borysenko, J. Z., Karnovsky, M. J. & Berlin, R. D. J. Cell Biol. 61, 70–82 (1974).
Taylor, R. B., Duffus, W. P. H., Raff, M. C. & de Petris, S. Nature new Biol. 233, 225–229 (1971).
Van Obberghen, E., De Meyts, P. & Roth, J. J. biol. Chem. 251, 6844–6851 (1976).
Edelman, G. M. Science 192, 218–226 (1976).
Stephens, R. E. & Edds, K. T. Physiol. Rev. 56, 218–226 (1976).
Malawista, S. E. Arthritis Rheum. 56, 709–711 (1976).
Gillespie, E. Ann. N.Y. Acad. Sci. 253, 771–779 (1975).
Dipasquale, A. M., McGuire, J., Moellmann, G. & Wasserman, S. J. J. Cell Biol. 71, 735–748 (1976).
Weissmann, G., Goldstein, I., Hoffstein, S. & Tsung, P. Ann. N.Y. Acad. Sci. 253, 750–762 (1975).
Willingham, M. C. & Pastan, I. J. Cell Biol. 67, 148–159 (1975).
Rubin, R. W. & Weiss, G. D. J. Cell Biol. 64, 42–53 (1975).
Puck, T. T. Proc. natn. Acad. Sci. U.S.A. 74, 4491–4495 (1977).
Gemsa, D., Steggemann, L., Till, G. & Resch, K. J. Immun. 119, 524–529 (1977).
Rudolph, S. A., Greengard, P. & Malawista, S. E. Proc. natn. Acad. Sci. U.S.A. 74, 3404–3408 (1977).
Iyengar, R., Lepper, K. G. & Mailman, D. S. J. supramolec. Struct. 5, 521–530 (1976).
Kaliner, M. J. clin. Invest. 60, 951–959 (1977).
Coffino, P. et al. Recent Prog. Horm. Res. 32, 669–682 (1976).
Maguire, M. E., Ross, E. M. & Gilman, A. G. in Advances in Cyclic Nucleotide Research 8 (eds Greengard P. & Robieson, G. A.) 1–84 (Raven, New York, 1977).
Shear, M., Insel, P. A., Melmon, K. L. & Coffino, P. J. biol. Chem. 251, 7572–7576 (1976).
Insel, P. A. in International Rev. of Biochemistry, series II, Biochemistry and Mode of Action of Hormones (ed. Rickenberg, H. V.) (University Park Press, Baltimore, in the press).
Mukherjee, C. & Lefkowitz, R. J. Life Sci. 19, 1897–1906 (1976).
Tallman, J. F., Smith, C. C. & Henneberry, R. C. Proc. natn. Acad. Sci. U.S.A. 72, 1564–1568 (1975).
Sheppard, J. R. Proc. natn. Acad. Sci. U.S.A. 74, 1091–1094 (1977).
Mukherjee, C., Caron, M. G., Coverstone, M. & Lefkowitz, R. J. J. biol. Chem. 251, 4869–4876 (1975).
Alexander, R. W., Williams, L. T. & Lefkowitz, R. J. Proc. natn. Acad. Sci. U.S.A. 72, 1564–1568 (1975).
Zatz, M., Kebabian, J. W., Romero, J. A., Lefkowitz, R. J. & Axelrod, J. J. Pharmac. exp. Ther. 196, 714–722 (1976).
Wolfe, B. B., Harden, T. K. & Molinoff, P. B. Ann. Rev. Pharmac. 17, 575–604 (1977).
Helmreich, E. J. M., Zenner, H. P., Pfeuffer, T. & Cori, C. F. in Current Topics in Cellular Regulation (eds Horecker, B. L. & Stadtman, E. R.) 10, 41–87 (Academic, New York, 1976).
Levitzki, A. Biochem. biophys. Res. Commun. 74, 1154–1159 (1977).
Rendell, M. S., Rodbell, M. & Berman, M. J. biol. Chem. 252, 7909–7912 (1977).
Cuatrecasas, P. & Hollenberg, M. D. Adv Protein Chem. 30, 251–451 (1976).
Greaves, M. F. Nature 265, 681–683 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
INSEL, P., KENNEDY, M. Colchicine potentiates β-adrenoreceptor-stimulated cyclic AMP in lymphoma cells by an action distal to the receptor. Nature 273, 471–473 (1978). https://doi.org/10.1038/273471a0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/273471a0
This article is cited by
-
G‐protein‐coupled receptors: past, present and future
British Journal of Pharmacology (2006)
-
Is signal transduction modulated by an interaction between heterotrimeric G-proteins and tubulin?
Endocrine (1997)
-
Roles of G protein subunits in transmembrane signalling
Nature (1988)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.