MgATP acts before Ca2+ to prime amylase secretion from permeabilized rat pancreatic acini

Padfield, Philip J.; Panesar, Ninder

doi:10.1152/ajpgi.1997.273.3.g655

Cited by 14 publications

(26 citation statements)

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“…The anoxia (N 2 bubbling) has already been reported not to affect [Ca 2ϩ ] i in non-ACh-stimulated and ACh-stimulated antral mucous cells (21). Thus the initial phase is induced by the fusion of the pooled primed granules, and the sustained phase is induced by the recruitment of granules to the apical membrane and the repriming of the exocytotic apparatus, as previously reported for pancreatic acinar cells and antral mucous cells (21,23). However, cGMP added before ATP depletion (by DNP or anoxia) induced an initial transient phase followed by a sustained phase in the ACh-stimulated exocytotic events.…”

Section: Discussionsupporting

confidence: 61%

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cGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells

Saad¹,

Shimamoto²,

Nakahari³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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In guinea pig antral mucous cells, ACh stimulates the Ca2+-regulated exocytosis, which has a characteristics feature: an initial transient phase followed by a sustained phase. The effects of cGMP on ACh-stimulated exocytosis were studied in guinea pig antral mucous cells using video microscopy. cGMP enhanced the frequency of ACh-stimulated exocytotic events, whereas cGMP alone did not induce any exocytotic events under the ACh-unstimulated condition. cGMP did not stimulate either Ca2+ mobilization or cAMP accumulation. The Ca2+ dose-response studies demonstrated that cGMP shifted the dose-response curve upward with no shift to the lower concentration. This indicates that cGMP increased maximal responsiveness of the Ca2+-regulated exocytosis, but not the Ca2+ sensitivity. Moreover, under a condition of ATP depletion by dinitrophenol (DNP) or anoxia (N2 bubbling), ACh evoked only a sustained phase in exocytotic events with no initial transient phase. However, ACh evoked an initial transient phase followed by a sustained phase with addition of cGMP before ATP depletion, whereas only a sustained phase was evoked in a case of cGMP addition after ATP depletion. Thus cGMP-induced enhancement in ACh-stimulated exocytotic events requires ATP, suggesting that cGMP modulates ATP-dependent priming of Ca2+-regulated exocytosis in antral mucous cells. In conclusion, cGMP increases the number of primed granules via acceleration of the ATP-dependent priming, which enhances the Ca2+-regulated exocytosis stimulated by ACh.

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Section: Discussionsupporting

confidence: 61%

“…The first step requires ATP, but not Ca 2ϩ , and primes granules with exocytotic machinery. The second step requires Ca 2ϩ , but not ATP, and triggers fusion of the granules to the apical membrane (23).…”

Section: Discussionmentioning

confidence: 99%

cGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells

Saad¹,

Shimamoto²,

Nakahari³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Exocytosis in many systems is assumed to consist of at least two distinct steps: priming of secretory granules and final fusion/exocytosis [3,10]. The results of our previous study suggested that a similar two-step mechanism, priming and fusion/exocytosis of amylase secretion, operates in rat parotid acinar cells.…”

Section: Introductionmentioning

confidence: 85%

Cyclic AMP has distinct effects from Ca 2+ in evoking priming and fusion/exocytosis in parotid amylase secretion

Yoshimura

Fujita-Yoshigaki

Murakami

et al. 2002

Pfl�gers Archiv European Journal of Physiology

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Rat parotid acinar cells were perfused in small quartz columns to examine the role of cAMP and Ca(2+) in the priming and fusion/exocytosis of amylase secretion. Carbachol (CCh) evoked a biphasic response of amylase secretion with an initial rapidly occurring large peak and a subsequent sustained plateau. Isoproterenol produced slowly increasing amylase secretion that reached the plateau greater than that induced by CCh. Combined stimulation with isoproterenol and CCh greatly potentiated amylase secretion. The rise and decay of amylase secretion induced by the combined stimulation was similar to those induced by CCh but not by isoproterenol, suggesting that the potentiation is caused by isoproterenol-induced modification of the CCh effect. Concentration-dependent responses of CCh-induced amylase secretion with and without isoproterenol showed that isoproterenol greatly enhances both the sensitivity and maximum effect of CCh. Similar potentiation was observed when the Ca(2+) effect was directly examined in cells permeabilized to Ca(2+) with ionomycin instead of CCh. In a Ca(2+)-free medium, CCh evoked an initial peak but did not produce a sustained plateau. Isoproterenol did not enhance the effect of CCh on [Ca(2+)](i). 2,4-Dintrophenol and carbonyl cyanide m-chlorophenyl hydrazone did not decrease the CCh-induced initial peak of amylase secretion but markedly decreased the sustained responses induced by isoproterenol and CCh. These results suggest that CCh, via Ca(2+), has two distinct effects on amylase secretion: triggering of fusion/exocytosis and the priming of secretory granules. Isoproterenol, via cyclic AMP, also has two distinct effects: direct stimulation of priming and enhancement of the sensitivity to the Ca(2+)effects. Thus, isoproterenol stimulates amylase secretion by increasing the primed pools of secretory granules, whereas CCh increases the flux of secretory granules into/from the primed pools, which is greatly enhanced by isoproterenol.

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“…Ca 2ϩ -regulated exocytosis in antral mucous cells consists of three biochemically distinct steps: docking, priming, and fusion. The priming step is regulated by ATP, and the fusion step is regulated by Ca 2ϩ (12,20,23). In antral mucous cells, Ca 2ϩ -regulated exocytosis has characteristic features of frequency: an initial peak that declines rapidly (initial phase or initial transient phase) followed by a second slower decline (late phase) lasting during acetylcholine (ACh) stimulation.…”

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confidence: 99%

A PKG inhibitor increases Ca²⁺-regulated exocytosis in guinea pig antral mucous cells: cAMP accumulation via PDE2A inhibition

Tanaka

Harada

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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In antral mucous cells, acetylcholine (ACh, 1 M) activates Ca 2ϩ -regulated exocytosis, consisting of an initial peak that declines rapidly (initial transient phase) followed by a second slower decline (late phase) lasting during ACh stimulation. The addition of 8-bromo-cGMP (8-BrcGMP) enhanced the initial phase, which was inhibited by the protein kinase G (PKG) inhibitor guanosine 3=,5=-cyclic monophosphorothoiate, ␤-phenyl-1,N 2 -etheno-8-bromo, Rp-isomer, sodium salt (Rp-8-BrPETcGMPS, 100 nM). However, Rp-8-BrPETcGMPS produced a delayed, but transient, increase in the exocytotic frequency during the late phase that was abolished by a protein kinase A (PKA) inhibitor (PKI-amide), suggesting that Rp-8-BrPETcGMPS accumulates cAMP. The cGMP-dependent phosphodiesterase 2 (PDE2), which degrades cAMP, may exist in antral mucous cells. The PDE2 inhibitor BAY-60-7550 (250 nM) mimicked the effect of Rp-8-BrPETcGMPS on ACh-stimulated exocytosis. Measurement of the cGMP and cAMP contents in antral mucosae revealed that ACh stimulates the accumulation of cGMP and that BAY-60-7550 accumulates cAMP similarly to Rp-8-BrPETcGMPS during ACh stimulation. Analyses of Western blot and immunohistochemistry demonstrated that PDE2A exists in antral mucous cells. In conclusion, Rp-8-BrPETcGMPS accumulates cAMP by inhibiting PDE2 in AChstimulated antral mucous cells, leading to the delayed, but transient, increase in the frequency of Ca 2ϩ -regulated exocytosis. PDE2 may prevent antral mucous cells from excessive mucin secretion caused by the cAMP accumulation.acetylcholine; guanosine 3=,5=-cyclic monophosphate; adenosine 3=,5=-cyclic monophosphate; gastric; mucin secretion GASTRIC MUCINS, WHICH ARE high-molecular-weight glycoproteins that protect the gastric mucosa from acid-peptic injury, are stored in intracellular granules and secreted to the lumen by Ca 2ϩ -regulated exocytosis. Ca 2ϩ -regulated exocytosis in antral mucous cells consists of three biochemically distinct steps: docking, priming, and fusion. The priming step is regulated by ATP, and the fusion step is regulated by Ca 2ϩ (12,20,23). In antral mucous cells, Ca 2ϩ -regulated exocytosis has characteristic features of frequency: an initial peak that declines rapidly (initial phase or initial transient phase) followed by a second slower decline (late phase) lasting during acetylcholine (ACh) stimulation. The initial phase, which is transient and has a high frequency of exocytotic events, is caused by an immediate fusion of the primed granules (the pool of releasable granules), and the late phase, which has a low frequency of exocytotic events, is caused by a fusion of granules that are in the process of priming (10).In antral mucous cells, Ca 2ϩ -regulated exocytosis is activated by ACh and is modulated by many substances, such as cAMP, cGMP, arachidonic acid (AA), and intracellular Cl Ϫ (3, 4, 10, 11, 14 -18). An accumulation of cAMP, which accelerates the priming step and the fusion step, also significantly increases the frequency of the initial phase in Ca 2ϩ -regulat...

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MgATP acts before Ca2+ to prime amylase secretion from permeabilized rat pancreatic acini

Cited by 14 publications

References 0 publications

cGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells

cGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells

Cyclic AMP has distinct effects from Ca 2+ in evoking priming and fusion/exocytosis in parotid amylase secretion

A PKG inhibitor increases Ca²⁺-regulated exocytosis in guinea pig antral mucous cells: cAMP accumulation via PDE2A inhibition

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MgATP acts before Ca2+ to prime amylase secretion from permeabilized rat pancreatic acini

Cited by 14 publications

References 0 publications

cGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells

cGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells

Cyclic AMP has distinct effects from Ca 2+ in evoking priming and fusion/exocytosis in parotid amylase secretion

A PKG inhibitor increases Ca2+-regulated exocytosis in guinea pig antral mucous cells: cAMP accumulation via PDE2A inhibition

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A PKG inhibitor increases Ca²⁺-regulated exocytosis in guinea pig antral mucous cells: cAMP accumulation via PDE2A inhibition