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Two roles for guanine nucleotides in the stimulus-secretion sequence of neutrophils

Two roles for guanine nucleotides in the stimulus-secretion sequence of neutrophils The term ’stimulus-secretion coupling‘ has, since first enunciated1, been held to involve the mobilization of cytosol Ca2+, which in turn is sufficient to trigger exocytotic secretory processes in metabolically competent cells. However, recent studies on a wide range of secretory cell types indicate that a role for Ca2+ can be obviated: examples are stimulation with phorbol ester (phorbol myristate acetate, PMA)2,3 which causes the activation of protein kinase C4 or the stimulation of platelets with collagen5. Ca2+-independent exocytosis also occurs when analogues of GTP are injected through the lumen of patch pipettes directly into the cytosol of mast cells6. The results presented here suggest that GTP analogues can activate secretory processes by actions at two distinct locations: one may be at the level of the receptor7 involving the activation of polyphos-phoinositide (PPI) phosphodiesterase8 with consequent liberation of diacylglycerol (DG)9; the other involves direct activation of the exocytotic mechanism. These conclusions are based on measurements of exocytotic secretion from permeabilized neutrophils into which we have been able to introduce, individually and in combination, Ca2+ chelators (EGTA and BAPTA), Ca2+ (buffered at micromolar concentrations with EGTA), analogues of GTP and GDP and the direct activator of protein kinase C, PMA. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

Two roles for guanine nucleotides in the stimulus-secretion sequence of neutrophils

Nature , Volume 319 (6053) – Feb 6, 1986

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References (34)

Publisher
Springer Journals
Copyright
Copyright © 1986 by Nature Publishing Group
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/319504a0
Publisher site
See Article on Publisher Site

Abstract

The term ’stimulus-secretion coupling‘ has, since first enunciated1, been held to involve the mobilization of cytosol Ca2+, which in turn is sufficient to trigger exocytotic secretory processes in metabolically competent cells. However, recent studies on a wide range of secretory cell types indicate that a role for Ca2+ can be obviated: examples are stimulation with phorbol ester (phorbol myristate acetate, PMA)2,3 which causes the activation of protein kinase C4 or the stimulation of platelets with collagen5. Ca2+-independent exocytosis also occurs when analogues of GTP are injected through the lumen of patch pipettes directly into the cytosol of mast cells6. The results presented here suggest that GTP analogues can activate secretory processes by actions at two distinct locations: one may be at the level of the receptor7 involving the activation of polyphos-phoinositide (PPI) phosphodiesterase8 with consequent liberation of diacylglycerol (DG)9; the other involves direct activation of the exocytotic mechanism. These conclusions are based on measurements of exocytotic secretion from permeabilized neutrophils into which we have been able to introduce, individually and in combination, Ca2+ chelators (EGTA and BAPTA), Ca2+ (buffered at micromolar concentrations with EGTA), analogues of GTP and GDP and the direct activator of protein kinase C, PMA.

Journal

NatureSpringer Journals

Published: Feb 6, 1986

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