Simulation of Regulated Exocytosis of Amylase from Salivary Parotid Acinar Cells by a Consecutive Reaction Model Comprising Two Sequential First-order Reactions

Fujita-Yoshigaki, Junko

doi:10.1006/jtbi.2000.2009

Cited by 10 publications

(12 citation statements)

References 41 publications

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“…Figure 7 shows the results of simulations of amylase secretion and of the size of the primed pools during stimulation with isoproterenol alone and with a combination of CCh and isoproterenol. The results of simulation, which were performed by the method developed by Fujita-Yoshigaki [4], are in good agreement with the considerations described above. Fig.…”

Section: Discussionsupporting

confidence: 65%

“…Our previous results suggest that a similar two-step model of amylase secretion operates in rat parotid acinar cells [4,20,22]. According to this model, the rate of amylase secretion is determined by the rate of the priming of secretory granules and the probability of a fusion event for each granule.…”

Section: Discussionmentioning

confidence: 97%

“…7 Simulation of time-dependent changes in amylase secretion and the size of the primed pools induced by isoproterenol and a combination of isoproterenol and CCh. Simulation was achieved by the method reported by Yoshigaki [4] based on the data of amylase secretion (Fig. 3a).…”

Section: Discussionmentioning

confidence: 99%

“…cAMP mainly stimulates amylase secretion by promoting the priming of secretory granules, thereby increasing the amount of secretary granules at the site of exocytosis, while CCh, via Ca 2+ , directly stimulates the final fusion/exocytosis of the primed granules [20,22]. Results of theoretical analysis of parotid amylase secretion based on the twostep model have recently been reported by Fujita-Yoshigaki [4].…”

Section: Introductionmentioning

confidence: 94%

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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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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

See 2 more Smart Citations

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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“…Acinar secretion proceeds as an initial peak phase within the first minute of stimulation and then declines to a plateau phase over several minutes, which is sustained in the presence of secretagogue (39). This pattern of exocytosis was first described using sequential secretory measures in isolated cells (40) and later quantified at the cellular level by membrane capacitance measures and differential interference contrast microscopy (41). Localization of VAMP 2 at the most apical aspects of acini is consistent with our previous report that VAMP 2-positive ZGs mediate the initial secretory response (22).…”

Section: Discussionmentioning

confidence: 99%

Complexin 2 Modulates Vesicle-associated Membrane Protein (VAMP) 2-regulated Zymogen Granule Exocytosis in Pancreatic Acini

Falkowski

Thomas

Groblewski

2010

Journal of Biological Chemistry

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Complexins are soluble proteins that regulate the activity of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes necessary for vesicle fusion. Neuronal specific complexin 1 has inhibitory and stimulatory effects on exocytosis by clamping trans-SNARE complexes in a prefusion state and promoting conformational changes to facilitate membrane fusion following cell stimulation. Complexins are unable to bind to monomeric SNARE proteins but bind with high affinity to ternary SNARE complexes and with lower affinity to target SNARE complexes. Far less is understood about complexin function outside the nervous system. Pancreatic acini express the complexin 2 isoform by RT-PCR and immunoblotting. Immunofluorescence microscopy revealed complexin 2 localized along the apical plasma membrane consistent with a role in secretion. Accordingly, complexin 2 was found to interact with vesicle-associated membrane protein (VAMP) 2, syntaxins 3 and 4, but not with VAMP 8 or syntaxin 2. Introduction of recombinant complexin 2 into permeabilized acini inhibited Ca 2؉ -stimulated secretion in a concentration-dependent manner with a maximal inhibition of nearly 50%. Mutations of the central ␣-helical domain reduced complexin 2 SNARE binding and concurrently abolished its inhibitory activity. Surprisingly, mutation of arginine 59 to histidine within the central ␣-helical domain did not alter SNARE binding and moreover, augmented Ca 2؉ -stimulated secretion by 130% of control. Consistent with biochemical studies, complexin 2 colocalized with VAMP 2 along the apical plasma membrane following cholecystokinin-8 stimulation. These data demonstrate a functional role for complexin 2 outside the nervous system and indicate that it participates in the Ca 2؉ -sensitive regulatory pathway for zymogen granule exocytosis.Complexin 1, originally identified as synaphin, is a small cytosolic protein that associates with soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, which are essential to drive membrane fusion during neurotransmitter exocytosis (1, 2). Although complexin 1 is expressed exclusively in neurons, complexin 2 appears to be ubiquitously expressed and presumably functions in other secretory cell systems. Complexins 1 and 2 are highly homologous, each containing 134 amino acids that are 86% identical (3). Moreover, rat, mouse, and human complexin 2 proteins are 100% identical, although the nucleotide sequences of their mRNAs are considerably different (4). Recently, two other isoforms, complexins 3 and 4, were identified; however, evidence of their specific function is unclear. Complexin 3 is expressed strongly in retina and certain regions of the brain including the hippocampus and thalamus, whereas complexin 4 is only expressed in retina (5).In neurons, the SNARE complex is a four-helical bundle composed of vesicle associated membrane protein (VAMP) 2 2, and the target SNAREs (t-SNAREs), syntaxin 1 and SNAP 25, located on the plasma membrane (6). Complexin 1 was orig...

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Elafin expression in human fetal and adult submandibular glands

Lee

Hirose

et al. 2002

Histochem Cell Biol

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Elafin, a bifunctional protein, has the NH(2)-terminal domain functions as a transglutaminase substrate for crosslinking to lysine-containing proteins and the COOH-terminal whey acidic protein domain as a potent anti-elastase. Human fetal submandibular glands (n=100) and adult submandibular glands (n=10) were used to elucidate the expression pattern of elafin in the developmental processes of human submandibular gland by immunohistochemistry, in situ hybridization, and western blot analysis. Elafin mRNA was expressed both in the gland epithelium and intralobular mesenchymal tissue of fetal submandibular gland in an early developmental stage (10-18 weeks) and an early intermediate developmental stage (EIDS; 19-24 weeks). The elafin antigen was also found in the intralobular mesenchyme of submandibular gland in the same stages. Thereafter, elafin was transitionally expressed in the ducts and acini of submandibular glands. In the late intermediate developmental stage (LIDS; 25-32 weeks) and the late developmental stage (LDS; 33-40 weeks), elafin became markedly positive in the excretory and striated ducts but weakly positive in the intralobular mesenchymal tissue. The elafin was heavily present in the excretory and striated ducts of adult submandibular gland, while it was sparse in the intralobular mesenchymal tissues. Western blot analysis showed the protein extracts from submandibular glands of EIDS, LIDS, and LDS, adult submandibular gland, fetal tissues (8 weeks), and adult parotid saliva migrated into multiple bands, about 25, 50, 65, and 140 kDa, which were higher than the putative size of elafin protein, 12 kDa. These data suggest that elafin, anti-elastase, is an essential component highly utilized during the morphogenetic processes of fetal salivary gland development and continuously plays a role for the protection of the tubuloalveolar structures of adult salivary gland.

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Simulation of Regulated Exocytosis of Amylase from Salivary Parotid Acinar Cells by a Consecutive Reaction Model Comprising Two Sequential First-order Reactions

Cited by 10 publications

References 41 publications

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

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

Complexin 2 Modulates Vesicle-associated Membrane Protein (VAMP) 2-regulated Zymogen Granule Exocytosis in Pancreatic Acini

Elafin expression in human fetal and adult submandibular glands

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