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.
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
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
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)
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.