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Neurotransmitter-induced inhibition of exocytosis in insulin-secreting beta cells by activation of calcineurin

Renström, Erik LU ; Ding, Wei-Guang; Bokvist, Krister and Rorsman, Patrik LU (1996) In Neuron 17(3). p.513-522
Abstract
Neurotransmitters and hormones such as somatostatin, galanin, and adrenalin reduce insulin secretion. Their inhibitory action involves direct interference with the exocytotic machinery. We have examined the molecular processes underlying this effect using high resolution measurements of cell capacitance. Suppression of exocytosis was maximal at concentrations that did not cause complete inhibition of glucose-stimulated electrical activity. This action was dependent on activation of G proteins but was not associated with inhibition of the voltage-dependent Ca2+ currents or adenylate cyclase activity. The molecular processes initiated by the agonists culminate in the activation of the Ca(2+)-dependent protein phosphatase calcineurin, and... (More)
Neurotransmitters and hormones such as somatostatin, galanin, and adrenalin reduce insulin secretion. Their inhibitory action involves direct interference with the exocytotic machinery. We have examined the molecular processes underlying this effect using high resolution measurements of cell capacitance. Suppression of exocytosis was maximal at concentrations that did not cause complete inhibition of glucose-stimulated electrical activity. This action was dependent on activation of G proteins but was not associated with inhibition of the voltage-dependent Ca2+ currents or adenylate cyclase activity. The molecular processes initiated by the agonists culminate in the activation of the Ca(2+)-dependent protein phosphatase calcineurin, and suppression of the activity of this enzyme abolishes their action on exocytosis. We propose that mechanisms similar to those we report here may contribute to adrenergic and peptidergic inhibition of secretion in other neuroendocrine cells and in nerve terminals. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Neuron
volume
17
issue
3
pages
513 - 522
publisher
Cell Press
external identifiers
  • pmid:8816714
  • scopus:0030245732
ISSN
0896-6273
DOI
10.1016/S0896-6273(00)80183-X
language
English
LU publication?
no
id
05931b28-bbe6-49a1-b21b-ad3f2c4c0a60 (old id 1109883)
date added to LUP
2008-07-29 09:52:56
date last changed
2017-06-11 03:27:49
@article{05931b28-bbe6-49a1-b21b-ad3f2c4c0a60,
  abstract     = {Neurotransmitters and hormones such as somatostatin, galanin, and adrenalin reduce insulin secretion. Their inhibitory action involves direct interference with the exocytotic machinery. We have examined the molecular processes underlying this effect using high resolution measurements of cell capacitance. Suppression of exocytosis was maximal at concentrations that did not cause complete inhibition of glucose-stimulated electrical activity. This action was dependent on activation of G proteins but was not associated with inhibition of the voltage-dependent Ca2+ currents or adenylate cyclase activity. The molecular processes initiated by the agonists culminate in the activation of the Ca(2+)-dependent protein phosphatase calcineurin, and suppression of the activity of this enzyme abolishes their action on exocytosis. We propose that mechanisms similar to those we report here may contribute to adrenergic and peptidergic inhibition of secretion in other neuroendocrine cells and in nerve terminals.},
  author       = {Renström, Erik and Ding, Wei-Guang and Bokvist, Krister and Rorsman, Patrik},
  issn         = {0896-6273},
  language     = {eng},
  number       = {3},
  pages        = {513--522},
  publisher    = {Cell Press},
  series       = {Neuron},
  title        = {Neurotransmitter-induced inhibition of exocytosis in insulin-secreting beta cells by activation of calcineurin},
  url          = {http://dx.doi.org/10.1016/S0896-6273(00)80183-X},
  volume       = {17},
  year         = {1996},
}