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1.
Trifluoperazine, chlorpromazine and other drugs to inhibit calmodulin-dependent processes are also known to inhibit protein kinase C. The effect of these agents on secretion evoked by known activators of C-kinase has been studied in human platelets loaded with the fluorescent Ca indicator, quin2 and preincubated with aspirin. The secretory response stimulated by phorbol ester and exogenous diacyglycerol, at basal levels of cytoplasmic free Ca2+, [Ca2+]i, was suppressed by trifluoperazine, chlorpromazine and W-7, as was the secretion evoked by collagen that occurs without a change in [Ca2+]i, The response to thrombin, which is accompanied by elevated [Ca2+]i was barely affected. Modest elevation of [Ca2+]i by Ca ionophore was able to overcome the inhibitory effect of these drugs on the response to phorbol ester, diacylglycerol, and collagen. 相似文献
2.
D. E. Knight 《Bioscience reports》1987,7(5):355-367
Measurements of intracellular Ca2+ in adrenal medullary cells suggest that a transient rise in Ca2+ leads to a transient secretory response, the rise in Ca2+ being brought about by an influx through voltage-sensitive Ca channels which subsequently inactivate. The level of Ca2+ observed is much smaller than the Ca2+ needed to trigger secretion when introduced directly into the cell. The discrepancy is removed by the presence of diacylglycerot, which increases the sensitivity of the secretory process to Ca2+. The site of action of Ca2+ and diacylglycerol is probably protein kinase C, and tile different secretory responses to increases of Ca2+ and diacylglycerol can be modelled in terms of a preferential order of binding of these two substrates to the enzyme. ATP is needed for secretion: one role is possibly to confer stability to the secretory apparatus; another may involve phosphorylation of some key protein. The kinetics of secretion suggest that if Ca2+ regulates phosphorylation or dephosphorylation, then it is therate of change of phosphorylation that controls secretion rather than theextent of phosphorylation or dephosphorylation. Guanine nucleotide-binding proteins may play a role not only at the level of signal transduction coupling, but also at or near the site of exocytosis, and the mechanism by which some Botulinum toxins inhibit secretion may be associated with these proteins. 相似文献
3.
Carole Muller Kamal Yassin Luo-Sheng Li Magnus Palmblad Suad Efendic Per-Olof Berggren Anthony Cerami Michael Brines Claes-G?ran ?stenson 《Molecular medicine (Cambridge, Mass.)》2015,21(1):969-978
Effects of ARA290 on glucose homeostasis were studied in type 2 diabetic Goto-Kakizaki (GK) rats. In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity. Glucose-stimulated insulin secretion was increased in islets from ARA290-treated rats. Additionally, in response to glucose, carbachol and KCl, islet cytoplasmic free Ca2+ concentrations, [Ca2+]i, were higher and the frequency of [Ca2+]i oscillations enhanced compared with placebo. ARA290 also improved stimulus–secretion coupling for glucose in GK rat islets, as shown by an improved glucose oxidation rate, ATP production and acutely enhanced glucose-stimulated insulin secretion. ARA290 also exerted an effect distal to the ATP-sensitive potassium (KATP) channel on the insulin exocytotic pathway, since the insulin response was improved following islet depolarization by KCl when KATP channels were kept open by diazoxide. Finally, inhibition of protein kinase A completely abolished effects of ARA290 on insulin secretion. In conclusion, ARA290 improved glucose tolerance without affecting hematocrit in diabetic GK rats. This effect appears to be due to improved β-cell glucose metabolism and [Ca2+]i handling, and thereby enhanced glucose-induced insulin release. 相似文献
4.
Calcium and cyclic nucleotide involvement in exocrine pancreatic enzyme secretion studied with the ionophore A-23187. 总被引:1,自引:0,他引:1
S Heisler 《Life sciences》1976,19(2):233-242
The ionophore, A-23187, was an effective pancreatic secretagogue. The response to A-23187 was Ca2+-dependent; Mg2+ reduced the secretory response to the ionophore. A-23187-stimulated enzyme release was potentiated by dibutyryl cyclic AMP; in the presence of carbachol, output of pancreatic protein paralleled the response to A-23187 alone. The time-course for secretion with A-23187 was similar to that observed with carbachol. The ionophore did not affect basal cyclic AMP levels but did stimulate a rapid Ca2+-dependent production of pancreatic cyclic GMP which preceded the onset of the secretory response. A-23187 did not significantly alter basal or carbachol-stimulated 45Ca efflux from isotope preloaded glands; yet in Ca2+-lowered media, it inhibited (reversed) the secretory response to carbachol, an effect which may have been due to an outward transport by the ionophore of cholinergic-mobilized intracellular Ca2+. Like carbachol, A-23187, inhibits the incorporation of amino acid into new protein, the effect being partially dependent on extracellular Ca2+. The data suggest that the pancreatic cholinergic receptor acts as a Ca2+-ionophore and that extracellular Ca2+ is utilized in the synthesis of cyclic GMP. 相似文献
5.
Rab3a is a small GTPase of the Rab3 subfamily that acts during late stages of Ca2+-regulated exocytosis. Previous functional analysis in pituitary melanotrophs described Rab3a as a positive regulator of Ca2+-dependent exocytosis. However, the precise role of the Rab3a isoform on the kinetics and intracellular [Ca2+] sensitivity of regulated exocytosis, which may affect the availability of two major peptide hormones, α-melanocyte stimulating hormone (α-MSH) and β-endorphin in plasma, remain elusive. We employed Rab3a knock-out mice (Rab3a KO) to explore the secretory phenotype in melanotrophs from fresh pituitary tissue slices. High resolution capacitance measurements showed that Rab3a KO melanotrophs possessed impaired Ca2+-triggered secretory activity as compared to wild-type cells. The hampered secretion was associated with the absence of cAMP-guanine exchange factor II/ Epac2-dependent secretory component. This component has been attributed to high Ca2+-sensitive release-ready vesicles as determined by slow photo-release of caged Ca2+. Radioimmunoassay revealed that α-MSH, but not β-endorphin, was elevated in the plasma of Rab3a KO mice, indicating increased constitutive exocytosis of α-MSH. Increased constitutive secretion of α-MSH from incubated tissue slices was associated with reduced α-MSH cellular content in Rab3a-deficient pituitary cells. Viral re-expression of the Rab3a protein in vitro rescued the secretory phenotype of melanotrophs from Rab3a KO mice. In conclusion, we suggest that Rab3a deficiency promotes constitutive secretion and underlies selective impairment of Ca2+-dependent release of α-MSH. 相似文献
6.
Stable enhancement of calcium retention in mitochondria isolated from rat liver after the administration of glucagon to the intact animal 总被引:11,自引:11,他引:0
1. Mitochondria isolated from rat liver by centrifugation of the homogenate in buffered iso-osmotic sucrose at between 4000 and 8000g-min, 1h after the administration in vivo of 30μg of glucagon/100g body wt., retain Ca2+ for over 45min after its addition at 100nmol/mg of mitochondrial protein in the presence of 2mm-Pi. In similar experiments, but after the administration of saline (0.9% NaCl) in place of glucagon, Ca2+ is retained for 6–8min. The ability of glucagon to enhance Ca2+ retention is completely prevented by co-administration of 4.2mg of puromycin/100g body wt. 2. The resting rate of respiration after Ca2+ accumulation by mitochondria from glucagon-treated rats remains low by contrast with that from saline-treated rats. Respiration in the latter mitochondria increased markedly after the Ca2+ accumulation, reflecting the uncoupling action of the ion. 3. Concomitant with the enhanced retention of Ca2+ and low rates of resting respiration by mitochondria from glucagon-treated rats was an increased ability to retain endogenous adenine nucleotides. 4. An investigation of properties of mitochondria known to influence Ca2+ transport revealed a significantly higher concentration of adenine nucleotides but not of Pi in those from glucagon-treated rats. The membrane potential remained unchanged, but the transmembrane pH gradient increased by approx. 10mV, indicating increased alkalinity of the matrix space. 5. Depletion of endogenous adenine nucleotides by Pi treatment in mitochondria from both glucagon-treated and saline-treated rats led to a marked diminution in ability to retain Ca2+. The activity of the adenine nucleotide translocase was unaffected by glucagon treatment of rats in vivo. 6. Although the data are consistent with the argument that the Ca2+-translocation cycle in rat liver mitochondria is a target for glucagon action in vivo, they do not permit conclusions to be drawn about the molecular mechanisms involved in the glucagon-induced alteration to this cycle. 相似文献
7.
J. Dinesh Kumar Chris Holmberg Silvia Balabanova Lyudmyla Borysova Ted Burdyga Robert Beynon Graham J. Dockray Andrea Varro 《PloS one》2015,10(10)
Mesenchymal stem cells (MSCs) play important roles in tissue repair and cancer progression. Our recent work suggests that some mesenchymal cells, notably myofibroblasts exhibit regulated exocytosis resembling that seen in neuroendocrine cells. We now report that MSCs also exhibit regulated exocytosis. Both a G-protein coupled receptor agonist, chemerin, and a receptor tyrosine kinase stimulant, IGF-II, evoked rapid increases in secretion of a marker protein, TGFβig-h3. The calcium ionophore, ionomycin, also rapidly increased secretion of TGFβig-h3 while inhibitors of translation (cycloheximide) or secretory protein transport (brefeldin A) had no effect, indicating secretion from preformed secretory vesicles. Inhibitors of the chemerin and IGF receptors specifically reduced the secretory response. Confocal microscopy of MSCs loaded with Fluo-4 revealed chemerin and IGF-II triggered intracellular Ca2+ oscillations requiring extracellular calcium. Immunocytochemistry showed co-localisation of TGFβig-h3 and MMP-2 to secretory vesicles, and transmission electron-microscopy showed dense-core secretory vesicles in proximity to the Golgi apparatus. Proteomic studies on the MSC secretome identified 64 proteins including TGFβig-h3 and MMP-2 that exhibited increased secretion in response to IGF-II treatment for 30min and western blot of selected proteins confirmed these data. Gene ontology analysis of proteins exhibiting regulated secretion indicated functions primarily associated with cell adhesion and in bioassays chemerin increased adhesion of MSCs and adhesion, proliferation and migration of myofibroblasts. Thus, MSCs exhibit regulated exocytosis that is compatible with an early role in tissue remodelling. 相似文献
8.
I.M. Shapiro A. Burke N.H. Lee 《Biochimica et Biophysica Acta (BBA)/General Subjects》1976,451(2):583-591
Previous morphological studies of the mineralizing epiphysis suggested that some mitochondria were concerned with Ca2+ accumulation while others were associated with cellular energetics and metabolism. To determine if there was mitochondrial heterogeneity in chondrocytes of the epiphyseal growth plate, mitochondria were isolated from four different regions of the plate and subjected to continuous sucrose gradient centrifugation. Centrifugation of the organelles in a narrow density sucrose gradient (1.5–2.0 M) in the presence of inhibitors of Ca2+ transport (ruthenium red and 5,5′-dithiobis-(2-nitrobenzoic acid)) revealed that considerable heterogeneity existed. In the least calcified zone 20% of the mitochondria formed a low density band of low Ca2+ concentration (309 nmol/mg protein). Organelles isolated from more calcified tissue zones showed a concomitant increase in Ca2+ concentration (up to 5700 nmol/mg protein) as well as an increase in the total percentage of mitochondria sedimenting in 2.0 M sucrose. The banding patterns of mitochondria isolated from rachitic and hypertrophic cartilage were similar. In addition, similarities were also noted in the Ca2+ concentration and the cytochrome oxidase activities of mitochondria of these tissues. During recovery from the rachitic condition, there was a change in the density centrifugation characteristics of this tissue and a substantial increase was noted in the proportion of mitochondria sedimenting in 2.0 M sucrose. The Ca2+ concentration of mitochondria of this rapidly calcifying tissue suggested that the critical Ca2+ concentration necessary for initiation of the calcification mechanism was 4 μmol/mg protein. 相似文献
9.
John Sargeant Danette Kowal Seiler Tucker Costain Corina T. Madreiter-Sokolowski David E. Gordon Andrew A. Peden Roland Malli Wolfgang F. Graier Jesse C. Hay 《The Journal of biological chemistry》2021,297(6)
ER-to-Golgi transport is the first step in the constitutive secretory pathway, which, unlike regulated secretion, is believed to proceed nonstop independent of Ca2+ flux. However, here we demonstrate that penta-EF hand (PEF) proteins ALG-2 and peflin constitute a hetero-bifunctional COPII regulator that responds to Ca2+ signaling by adopting one of several distinct activity states. Functionally, these states can adjust the rate of ER export of COPII-sorted cargos up or down by ∼50%. We found that at steady-state Ca2+, ALG-2/peflin hetero-complexes bind to ER exit sites (ERES) through the ALG-2 subunit to confer a low, buffered secretion rate, while peflin-lacking ALG-2 complexes markedly stimulate secretion. Upon Ca2+ signaling, ALG-2 complexes lacking peflin can either increase or decrease the secretion rate depending on signaling intensity and duration—phenomena that could contribute to cellular growth and intercellular communication following secretory increases or protection from excitotoxicity and infection following decreases. In epithelial normal rat kidney (NRK) cells, the Ca2+-mobilizing agonist ATP causes ALG-2 to depress ER export, while in neuroendocrine PC12 cells, Ca2+ mobilization by ATP results in ALG-2-dependent enhancement of secretion. Furthermore, distinct Ca2+ signaling patterns in NRK cells produce opposing ALG-2-dependent effects on secretion. Mechanistically, ALG-2-dependent depression of secretion involves decreased levels of the COPII outer shell and increased peflin targeting to ERES, while ALG-2-dependent enhancement of secretion involves increased COPII outer shell and decreased peflin at ERES. These data provide insights into how PEF protein dynamics affect secretion of important physiological cargoes such as collagen I and significantly impact ER stress. 相似文献
10.
Ca2+ is now firmly established as the most important intracellular regulator of physiological and pathological events in a vast number of different cell types, including secretory epithelia. In these tissues, Ca2+ signalling is crucially important for the control of both fluid secretion and electrolyte secretion as well as the regulation of macromolecule secretion. In this overview article, I shall attempt to give some general background to the concepts underlying our current thinking about Ca2+ signalling in epithelia and its roles in regulating secretion. It is outside the scope of this review to provide a comprehensive account of Ca2+ signalling and the many different processes in the many different secretory epithelia that are controlled by Ca2+ signals. It is my aim to draw attention to some general features of Ca2+ signalling processes in secretory epithelia, which are rather different from those in, for example, endocrine glands. The principal examples will be taken from studies of exocrine cells and, in particular, pancreatic acinar cells, as they are the pioneer cells with regard to investigations of Ca2+ signalling due to primary intracellular Ca2+ release. They also represent the cell type which has been characterized in most detail with regard to Ca2+ transport events and mechanisms. 相似文献
11.
Peter Nygren 《Bioscience reports》1986,6(12):1057-1063
Monolayer culture of bovine parathyroid cells for 24 hours resulted in a right-shift of the dose-effect relationships for Ca2+-inhibition of parathyroid hormone (PTH) release and the dependence of the cytoplasmic Ca2+ concentration (Ca2+) on extracellular Ca2+ as well as in a less suppressible hormone release. After 4 days of culture, hormone secretion was almost non-suppressible and Ca
i
2+
increased poorly in response to a rise in extracelluiar Ca2+. Ionomycin, a Ca2+ ionophore, raised Ca
i
2+
, but there was only a small inhibition of PTH release and the correlation between Ca
i
2+
and secretion was weak. A deteriorated Ca
i
2+
regulation and a decreased inhibitory action of cytoplasmic Ca2+ on PTH release were also found in ceils from human parathyroid adenomas. Functional dedifferentiation of the parathyroid cell thus results from both defective regulation and action of cytoplasmic Ca2+. 相似文献
12.
Ca2+ flux into mitochondria is an important regulator of cytoplasmic Ca2+ signals, energy production and cell death pathways. Ca2+ uptake can occur through the recently discovered mitochondrial uniporter channel (MCU) but whether the MCU is involved in shaping Ca2+ signals and downstream responses to physiological levels of receptor stimulation is unknown. Here, we show that modest stimulation of leukotriene receptors with the pro-inflammatory signal LTC4 evokes a series of cytoplasmic Ca2+ oscillations that are rapidly and faithfully propagated into mitochondrial matrix. Knockdown of MCU or mitochondrial depolarisation, to reduce the driving force for Ca2+ entry into the matrix, prevents the mitochondrial Ca2+ rise and accelerates run down of the oscillations. The loss of cytoplasmic Ca2+ oscillations appeared to be a consequence of enhanced Ca2+-dependent inactivation of InsP3 receptors, which arose from the loss of mitochondrial Ca2+ buffering. Ca2+ dependent gene expression in response to leukotriene receptor activation was suppressed following knockdown of the MCU. In addition to buffering Ca2+ release, mitochondria also sequestrated Ca2+ entry through store-operated Ca2+ channels and this too was prevented following loss of MCU. MCU is therefore an important regulator of physiological pulses of cytoplasmic Ca2+. 相似文献
13.
Manganese (2.2mM) blocked catecholamine (CA) secretion evoked by acetylcholine (ACh) in perfused bovine adrenals. This effect was reverted when the concentration of Mn2+ was increased to 6.6mM. Similar results were observed when higher concentrations (11 and 22mM respectively) were used. Mn2+ substituted for Ca2+ in the ACh evoked CA secretion, and this response was concentration dependent. The removal of Mn2+ from the perfusion medium potentiated the secretory response with respect to the first ACh stimulation. The subcellular distribution of Mn2+ in perfused adrenals showed a poor association with storage granules. It is concluded that Mn2+ inhibits Ca2+ entry during secretion and also substitutes for Ca2+ in the excitation-secretion coupling. 相似文献
14.
Yoo SH 《Cell calcium》2011,50(2):175-183
The majority of secretory cell calcium is stored in secretory granules that serve as the major IP3-dependent intracellular Ca2+ store. Even in unicellular phytoplankton secretory granules are responsible for the IP3-induced Ca2+ release that triggers exocytosis. The number of secretory granules in the cell is directly related not only to the magnitude of IP3-induced Ca2+ release, which accounts for the majority of the IP3-induced cytoplasmic Ca2+ release in neuroendocrine cells, but also to the IP3 sensitivity of the cytoplasmic IP3 receptor (IP3R)/Ca2+ channels. Moreover, secretory granules contain the highest IP3R concentrations and the largest amounts of IP3Rs in any subcellular organelles in neuroendocrine cells. Secretory granules from phytoplankton to mammals contain large amounts of polyanionic molecules, chromogranins being the major molecules in mammals, in addition to acidic intragranular pH and high Ca2+ concentrations. The polyanionic molecules undergo pH- and Ca2+-dependent conformational changes that serve as a molecular basis for condensation-decondensation phase transitions of the intragranular matrix. Likewise, chromogranins undergo pH- and Ca2+-dependent conformational changes with increased exposure of the structure and increased interactions with Ca2+ and other granule components at acidic pH. The unique physico-chemical properties of polyanionic molecules appear to be at the center of biogenesis, and physiological functions of secretory granules in living organisms from primitive to advanced species. 相似文献
15.
16.
Olga Kopach Ilya Kruglikov Tatyana Pivneva Nana Voitenko Alexei Verkhratsky Nataliya Fedirko 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(10):1740-1748
The salivary acinar cells have unique Ca2+ signaling machinery that ensures an extensive secretion. The agonist-induced secretion is governed by Ca2+ signals originated from the endoplasmic reticulum (ER) followed by a store-operated Ca2+ entry (SOCE). During tasting and chewing food a frequency of parasympathetic stimulation increases up to ten fold, entailing cells to adapt its Ca2+ machinery to promote ER refilling and ensure sustained SOCE by yet unknown mechanism. By employing a combination of fluorescent Ca2+ imaging in the cytoplasm and inside cellular organelles (ER and mitochondria) we described the role of mitochondria in adjustment of Ca2+ signaling regime and ER refilling according to a pattern of agonist stimulation. Under the sustained stimulation, SOCE is increased proportionally to the degree of ER depletion. Cell adapts its Ca2+ handling system directing more Ca2+ into mitochondria via microdomains of high [Ca2+] providing positive feedback on SOCE while intra-mitochondrial tunneling provides adequate ER refilling. In the absence of an agonist, the bulk of ER refilling occurs through Ca2+-ATPase-mediated Ca2+ uptake within subplasmalemmal space. In conclusion, mitochondria play a key role in the maintenance of sustained SOCE and adequate ER refilling by regulating Ca2+ fluxes within the cell that may represent an intrinsic adaptation mechanism to ensure a long-lasting secretion. 相似文献
17.
Abstract. The albumen gland of the freshwater pulmonate snail Helisoma duryi produces and secretes the perivitelline fluid, which coats fertilized eggs and provides nutrients to the developing embryos. It is known that perivitelline fluid secretion is stimulated by dopamine through the activation of a dopamine D1‐like receptor, which in turn stimulates cAMP production leading to the secretion of perivitelline fluid. This paper examines the glandular release of perivitelline fluid and provides evidence for the role of Ca2+ in the regulated secretion of perivitelline fluid based on protein secretion experiments and inositol 1,4,5‐trisphosphate assays. Dopamine‐stimulated protein secretion by the albumen gland is reduced in Ca2+‐free medium or in the presence of plasma membrane Ca2+ channel blockers, although the Ca2+ channel subtype involved is unclear. In addition, dopamine‐stimulated protein secretion does not directly involve phospholipase C‐generated signaling pathways and Ca2+ release from intracellular stores. Sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase inhibitors had little effect on protein secretion when applied alone; however, they potentiated dopamine‐stimulated protein secretion. Dantrolene, an inhibitor of ryanodine receptors, 8‐(N,N‐diethylamino)‐octyl‐3,4,5‐trimethoxybenzoate hydrochloride, a nonspecific inhibitor of intracellular Ca2+ channels, and 2‐aminoethyldiphenylborate, an inhibitor of inositol 1,4,5‐trisphosphate receptors, did not suppress protein secretion, suggesting Ca2+ release from internal stores does not directly regulate protein secretion. Thus, the influx of Ca2+ from the extracellular space appears to be the major pathway mediating protein secretion by the albumen gland. The results are discussed with respect to the role of Ca2+ in controlling exocytosis of proteins from the albumen gland secretory cells. 相似文献
18.
Previous morphological studies of the mineralizing epiphysis suggested that some mitochondria were concerned with Ca2+ accumulation while others were associated with cellular energetics and metabolism. To determine if there was mitochondrial heterogeneity in chondrocytes of the epiphyseal growth plate, mitochondria were isolated from four different regions of the plate and subjected to continuous sucrose gradient centrifugation. Centrifugation of the organelles in a narrow density sucrose gradient (1.5–2.0 M) in the presence of inhibitors of Ca2+ transport (ruthenium red and 5,5′-dithiobis-(2-nitrobenzoic acid)) revealed that considerable heterogeneity existed. In the least calcified zone 20% of the mitochondria formed a low density band of low Ca2+ concentration (309 nmol/mg protein). Organelles isolated from more calcified tissue zones showed a concomitant increase in Ca2+ concentration (up to 5700 nmol/mg protein) as well as an increase in the total percentage of mitochondria sedimenting in 2.0 M sucrose. The banding patterns of mitochondria isolated from rachitic and hypertrophic cartilage were similar. In addition, similarities were also noted in the Ca2+ concentration and the cytochrome oxidase activities of mitochondria of these tissues. During recovery from the rachitic condition, there was a change in the density centrifugation characteristics of this tissue and a substantial increase was noted in the proportion of mitochondria sedimenting in 2.0 M sucrose. The Ca2+ concentration of mitochondria of this rapidly calcifying tissue suggested that the critical Ca2+ concentration necessary for initiation of the calcification mechanism was 4 μmol/mg protein. 相似文献
19.
Jean-Denis Troadec Sylvie Thirion Jean-Pierre Laugier Ghislain Nicaise 《Biology of the cell / under the auspices of the European Cell Biology Organization》1998,90(4):339-347
Digitonin-permeabilized isolated neurohypophysial nerve terminals are known to release their secretory vesicle content under calcium challenge. On this preparation, we monitored intra-organelle Ca2+ concentration using digital fluorescence microscopy of Fura-2. The superfusion of artificial intracellular solution containing 10 to 50 μM Ca2+ induced an intra-organelle [Ca2+] increase. Two major organelles are candidates for this increase: secretory vesicles and mitochondria. In an attempt to detect calcium changes in the vesicles, ruthenium red was used to impair mitochondrial calcium uptake. Part of the ruthenium red-insensitive intra-organelle [Ca2+] increase was abolished by raising sodium in the solution. Removing sodium boosted the intra-organelle [Ca2+] increase. These results taken together suggest the participation of Na/Ca exchange, known to exist in the membrane of these secretory vesicles. In addition to Na/Ca exchange, there would be at least another mechanism of vesicular calcium intake, as suggested by the partial inhibition of intra-organelle [Ca2+] increase obtained under acidic compartments: neutralization with NH4Cl. This mechanism remains to be defined. The main conclusion presented here, that an intravesicular [Ca2+] increase takes place at the rate of secretion, was predicted by the hypothesis that intravesicular Ca2+ changes would be involved in stimulus-secretion coupling. 相似文献
20.
This brief review discusses recent advances in studies of mitochondrial Ca2+ signaling and considers how the relationships between mitochondria and Ca2+ responses are shaped in secretory epithelial cells. Perhaps the more precise title of this review could have been “How to win ATP and influence Ca2+ signaling in secretory epithelium with emphasis on exocrine secretory cells and specific focus on pancreatic acinar cells”. But “brevity is a virtue” and the authors hope that many of the mechanisms discussed are general and applicable to other tissues and cell types. Among these mechanisms are mitochondrial regulation of Ca2+ entry and the role of mitochondria in the formation of localized Ca2+ responses. The roles of Ca2+ signaling in the physiological adjustment of bioenergetics and in mitochondrial damage are also briefly discussed. 相似文献