Abstract
THE neuropeptide somatostatin inhibits secretion from electrically excitable cells in the pituitary, pancreas, gut and brain1. In mammalian pituitary tumour cells somatostatin inhibits secretion through two distinct pertussis toxin-sensitive mechanisms2–5. One involves inhibition of adenylyl cyclase6, the other an unidentified cyclic AMP-independent mechanism that reduces Ca2+ influx7,8 by increasing membrane conductance to potassium9,10. Here we demonstrate that the predominant electrophysiological effect of somatostatin on metabolically intact pituitary tumour cells is a large, sustained increase in the activity of the large-conductance Ca2+- and voltage-activated K+ channels (BK). This action of somatostatin does not involve direct effects of Ca2+, cAMP or G proteins on the channels. Our results indicate instead that somato-statin stimulates BK channel activity through protein dephosphorylation.
Similar content being viewed by others
References
Patel, Y. & Tannenbaum, G. S. (eds) Metabolism 39, Suppl. 2, 1–191 (1990).
Dorflinger, L. J. & Schonbrunn, A. Endocrinology 113, 1541–1550 (1983).
Dorflinger, L. J. & Schonbrunn, A. Endocrinology 113, 1551–1558 (1983).
Koch, B., Dorflinger, L. J. & Schonbrunn, A. J. biol. Chem. 260, 13138–13145 (1985).
Yajima, Y., Akita, Y. & Saito, T. J. biol. Chem. 261, 2684–2689 (1986).
Koch, B. & Schonbrunn, A. Endocrinology 114, 1784–1790 (1984).
Schlegel, W., Wuarin, F., Wollheim, C. B. & Zahnd, G. R. Cell Calcium 5, 223–236 (1984).
Schlegel, W. et al. Nature 329, 719–721 (1987).
Koch, B. D., Blalock, J. B. & Schonbrunn, A. J. biol. Chem. 263, 216–225 (1988).
Koch, B. D. & Schonbrunn, A. J. biol. Chem. 263, 226–234 (1988).
Luini, A., Lewis, D., Guild, S., Schofield, G. & Weight, F. J. Neurosci. 6, 3128–3132 (1986).
Yamashita, N., Shibuya, N. & Ogata, E. Proc. natn. Acad. Sci. U.S.A. 83, 6198–6202 (1986).
Mollard, P., Vacher, P., Dufy, B. & Barker, J. L. Endocrinology 123, 721–732 (1988).
Lewis, D. L., Weight, F. F. & Luini, A. Proc. natn. Acad. Sci. U.S.A. 83, 9035–9039 (1986).
Rosenthal, W. et al. EMBO J. 7, 1627–1633 (1988).
Yamashita, N., Shibuya, N. & Ogata, E. Proc. natn. Acad. Sci. U.S.A. 85, 4924–4928 (1988).
Horn, R. & Marty, A. J. gen. Physiol. 92, 145–159 (1988).
Korn, S. J. & Horn, R. J. gen. Physiol. 94, 789–812 (1989).
Kalman, D., O'Lague, P., Erxleben, C. & Armstrong, D. J. gen. physiol. 92, 531–548 (1988).
Enyeart, J. J., Aizawa, T. & Hinkle, P. M. Am. J. Physiol. 248, C510–C519 (1985).
Dubinsky, J. M. & Oxford, G. S. J. gen. Physiol. 83, 309–339 (1984).
Ritchie, A. K. J. Physiol. (Lond.) 385, 591–609 (1987).
Latorre, R., Oberhauser, A., Labarca, P. & Alvarez, O. A. Rev. Physiol. 51, 385–399 (1989).
Miller, C., Moczydlowski, E., Latorre, R. & Phillips, M. Nature 313, 316–318 (1988).
Pfeuffer, T. & Helmreich, E. J. M. Curr. Top. cell. Reg. 29, 129–216 (1988).
Yatani, A., Codina, J., Sekura, R. D., Birnbaumer, L. & Brown, A. M. Molec. Endocr. 1, 283–289 (1987).
Toro, L., Ramos-Franco, J. & Stefani, E. J. gen. Physiol. 96, 373–394 (1990).
Maruyama, Y. & Petersen, O. H. Nature 300, 61–63 (1982).
Ewald, D. A., Williams, A. & Levitan, I. B. Nature 315, 503–506 (1985).
Lechleiter, J. D., Dartt, D. A. & Brehm, P. Neuron 1, 27–235 (1988).
Kume, H., Takai, A., Tokumo, H. & Tomita, T. Nature 341, 152–154 (1989).
Sikdar, S. K., Mclntosh, R. P. & Mason, W. T. Brain Res. 496, 113–123 (1989).
Bialojan, C. & Takai, A. Biochem. J. 256, 283–290 (1988).
Cohen, P. A. Rev. Biochem. 58, 453–508 (1989).
Armstrong, D. & Eckert, R. Proc. natn. Acad. Sci. U.S.A. 84, 2518–2522 (1987).
Armstrong, D. L. Trends Neurosci. 12, 117–122 (1989).
Reinhart, P. H., Chung, S., Martin, B. L., Brautigan, D. L. & Levitan, I. B. J. Neurosci. (in the press).
Liebow, C., Reilly, C., Serrano, M. & Schally, A. V. Proc. natn. Acad. Sci. U.S.A. 86, 2003–2007 (1989).
Tashjian Jr, A. H. Meth. Enzym. 58, 527–535 (1979).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
White, R., Schonbrunn, A. & Armstrong, D. Somatostatin stimulates Ca2+-activated K+ channels through protein dephosphorylation. Nature 351, 570–573 (1991). https://doi.org/10.1038/351570a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/351570a0
- Springer Nature Limited
This article is cited by
-
A novel BK channel-targeted peptide suppresses sound evoked activity in the mouse inferior colliculus
Scientific Reports (2017)
-
Somatostatin and dopamine receptor regulation of pituitary somatotroph adenomas
Pituitary (2017)
-
High-conductance potassium channels of the SLO family
Nature Reviews Neuroscience (2006)
-
Outward current produced by somatostatin (SRIF) in rat anterior cingulate pyramidal cells in vitro
British Journal of Pharmacology (1998)
-
Somatostatin receptors in Neuro2A neuroblastoma cells: operational characteristics
British Journal of Pharmacology (1997)