scholarly journals Ca2+ release triggered by NAADP in hepatocyte microsomes

2006 ◽  
Vol 395 (2) ◽  
pp. 233-238 ◽  
Author(s):  
Miklós Mándi ◽  
Balázs Tóth ◽  
György Timár ◽  
Judit Bak
Keyword(s):  
Nicotinic Acid ◽  
Ryanodine Receptor ◽  
Sea Urchin ◽  
Mammalian Cells ◽  
Liver Microsomes ◽  
The Other ◽  
Release Mechanism ◽  
Ip3 Receptors ◽  
Rat Hepatocyte ◽  
Inositol 1,4,5 Trisphosphate

NAADP (nicotinic acid–adenine dinucleotide phosphate) is fast emerging as a new intracellular Ca2+-mobilizing messenger. NAADP induces Ca2+ release by a mechanism that is distinct from IP3 (inositol 1,4,5-trisphosphate)- and cADPR (cADP-ribose)-induced Ca2+ release. In the present study, we demonstrated that micromolar concentrations of NAADP trigger Ca2+ release from rat hepatocyte microsomes. Cross-desensitization to IP3 and cADPR by NAADP did not occur in liver microsomes. We report that non-activating concentrations of NAADP can fully inactivate the NAADP-sensitive Ca2+-release mechanism in hepatocyte microsomes. The ability of thapsigargin to block the NAADP-sensitive Ca2+ release is not observed in sea-urchin eggs or in intact mammalian cells. In contrast with the Ca2+ release induced by IP3 and cADPR, the Ca2+ release induced by NAADP was completely independent of the free extravesicular Ca2+ concentration and pH (in the range 6.4–7.8). The NAADP-elicited Ca2+ release cannot be blocked by the inhibitors of the IP3 receptors and the ryanodine receptor. On the other hand, verapamil and diltiazem do inhibit the NAADP- (but not IP3- or cADPR-) induced Ca2+ release.

NAADP, a new intracellular messenger that mobilizes Ca2+ from acidic stores

2006 ◽  
Vol 34 (5) ◽  
pp. 922-926 ◽  
Author(s):  
A. Galione
Keyword(s):  
Sea Urchin ◽  
Mammalian Cells ◽  
Ryanodine Receptors ◽  
Release Mechanism ◽  
Release Channel ◽  
Sea Urchin Egg ◽  
Wide Range ◽  
Inositol 1,4,5 Trisphosphate ◽  
Molecular Nature ◽  
Made In

NAADP (nicotinic acid–adenine dinucleotide phosphate) is a recently described Ca2+-mobilizing molecule. First characterized in the sea urchin egg, it has been shown to mobilize Ca2+ from intracellular stores in a wide range of cells from different organisms. It is a remarkably potent molecule, and recent reports show that its cellular levels change in response to a variety of agonists, confirming its role as a Ca2+-mobilizing messenger. In many cases, NAADP appears to interact with other Ca2+-mobilizing messengers such as IP3 (inositol 1,4,5-trisphosphate) and cADP-ribose in shaping cytosolic Ca2+ signals. What is not clear is the molecular nature of the NAADP-sensitive Ca2+ release mechanism and its subcellular localization. This review focuses on the recent progress made in sea urchin eggs, which indicates that NAADP activates a novel Ca2+ release channel distinct from the relatively well-characterized IP3 and ryanodine receptors. Furthermore, in the sea urchin egg, the NAADP-sensitive store appears to be separate from the endoplasmic reticulum and is most likely an acidic store. These findings have also been reinforced by similar findings in mammalian cells, and a unified model for NAADP-induced Ca2+ signalling is presented.

Mechanisms of calcium signaling by cyclic ADP-ribose and NAADP

1997 ◽  
Vol 77 (4) ◽  
pp. 1133-1164 ◽  
Author(s):  
H. C. Lee
Keyword(s):  
Nitric Oxide ◽  
Nicotinic Acid ◽  
Live Cells ◽  
Release Mechanism ◽  
Major Mechanism ◽  
Signaling Mechanisms ◽  
Signaling Function ◽  
Cyclic Adp Ribose ◽  
Inositol 1,4,5 Trisphosphate ◽  
External Signals

Cells possess various mechanisms for transducing external signals to intracellular responses. The discovery of inositol 1,4,5-trisphosphate (IP3) as a messenger for mobilizing internal Ca2+ stores has centralized Ca2+ mobilization among signaling mechanisms. Results reviewed in this article establish that, in addition to IP3, the internal Ca2+ stores can be mobilized by at least two other molecules, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), via totally independent mechanisms. Cyclic ADP-ribose is a newly discovered cyclic nucleotide derived from NAD, but, unlike adenosine 3',5'-cyclic monophosphate, its main signaling function is modulation of Ca(2+)-induced Ca2+ release, a major mechanism of Ca2+ mobilization in addition to the IP3 pathway. Evidence shows that cADPR may in fact be responsible for mediating the Ca(2+)-mobilizing activity of the gaseous messenger nitric oxide. Cells responsive to cADPR are widespread and include species from plant to mammal, indicating the generality of cADPR as a signaling molecule. In addition to cADPR, NAADP, a metabolite of NADP, can also mobilize Ca2+ stores. The release mechanism and the stores on which NAADP acts are distinct from cADPR and IP3. Nicotinic acid adenine dinucleotide phosphate may play a role in generating Ca2+ oscillations, since liberation of NAADP in live cells by photolyzing its caged analog produces long lasting Ca2+ oscillations. These two new Ca2+ agonists are intimately related, since the same metabolic enzymes can, under appropriate conditions, synthesize either one, suggesting a unified mechanism may regulate both pathways. Elucidation of these two new Ca2+ mobilization pathways is likely to have an important impact on our understanding of cellular signaling mechanisms.

Requirement for a localized, IP3R-generated Ca2+ transient during the furrow positioning process in zebrafish zygotes

Zygote ◽  
2006 ◽  
Vol 14 (2) ◽  
pp. 143-155 ◽  
Author(s):  
Karen W. Lee ◽  
Sarah E. Webb ◽  
Andrew L. Miller
Keyword(s):  
The Other ◽  
Release Mechanism ◽  
Cleavage Furrow ◽  
Specific Function ◽  
Free Medium ◽  
Initial Transient ◽  
Absolute Requirement ◽  
Inositol 1,4,5 Trisphosphate ◽  
Subsequent Propagation ◽  
Trisphosphate Receptor

SummaryWe report that the first localized Ca2+ transient visualized in the blastodisc cortex of post-mitotic zebrafish zygotes has unique features. We confirm that this initial ‘furrow positioning’ Ca2+ transient precedes the physical appearance of the first cleavage furrow at the blastodisc surface and that it has unique dynamics, which distinguish it from the subsequent furrow propagation transients that develop from it. This initial transient displays a distinct rising phase that peaks prior to the initiation of the two linear, subsurface, self-propagating Ca2+ waves that constitute the subsequent furrow propagation transient. Through the carefully timed introduction of the Ca2+ buffer, dibromo-BAPTA, we also demonstrate the absolute requirement of this initial rising phase Ca2+ transient in positioning the furrow at the blastodisc surface: no rising phase transient, no cleavage furrow. Likewise, the introduction of the inositol 1,4,5-trisphosphate receptor (IP3R) antagonist, 2-aminoethoxydiphenyl borate, eliminates both the rising phase transient and the appearance of the furrow at the cell surface. On the other hand, antagonists of the ryanodine receptor and NAADP-sensitive channels, or simply bathing the zygote in Ca2+-free medium, have no effect on the generation of the rising phase positioning transient or the appearance of the furrow at the surface. This suggests that like the subsequent propagation and deepening/zipping Ca2+ transients, the rising phase furrow positioning transient is also generated specifically by Ca2+ released via IP3Rs. We propose, however, that despite being generated by a similar Ca2+ release mechanism, the unique features of this initial transient suggest that it might be a distinct signal with a specific function associated with positioning the cleavage furrow at the blastodisc surface.

Increase of cGMP, cADP-ribose and inositol 1,4,5-trisphosphate preceding Ca2+ transients in fertilization of sea urchin eggs

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4405-4414 ◽  
Author(s):  
Ritsu Kuroda ◽  
Kenji Kontani ◽  
Yasunari Kanda ◽  
Toshiaki Katada ◽  
Takashi Nakano ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Sea Urchin ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Sea Urchin Eggs ◽  
Direct Measurements ◽  
Cyclic Adp Ribose ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor ◽  
Receptor Channel

Transient increases, or oscillations, of cytoplasmic free Ca2+ concentration, [Ca2+]i, occur during fertilization of animal egg cells. In sea urchin eggs, the increased Ca2+ is derived from intracellular stores, but the principal signaling and release system involved has not yet been agreed upon. Possible candidates are the inositol 1,4,5-trisphosphate receptor/channel (IP3R) and the ryanodine receptor/channel (RyR) which is activated by cGMP or cyclic ADP-ribose (cADPR). Thus, it seemed that direct measurements of the likely second messenger candidates during sea urchin fertilization would be essential to an understanding of the Ca2+ signaling pathway. We therefore measured the cGMP, cADPR and inositol 1,4,5-trisphosphate (IP3) contents of sea urchin eggs during the early stages of fertilization and compared these with the [Ca2+]i rise in the presence or absence of an inhibitor against soluble guanylate cyclase. We obtained three major experimental results: (1) cytosolic cGMP levels began to rise first, followed by cADPR and IP3 levels, all almost doubling before the explosive increase of [Ca2+]i; (2) most of the rise in IP3 occurred after the Ca2+ peak; IP3 production could also be induced by the artificial elevation of [Ca2+]i, suggesting the large increase in IP3 is a consequence, rather than a cause, of the Ca2+ transient; (3) the measured increase in cGMP was produced by the soluble guanylate cyclase of eggs, and inhibition of soluble guanylate cyclase of eggs diminished the production of both cADPR and IP3 and the [Ca2+]i increase without the delay of Ca2+ transients. Taken together, these results suggest that the RyR pathway involving cGMP and cADPR is not solely responsible for the initiating event, but contributes to the Ca2+ transients by stimulating IP3 production during fertilization of sea urchin eggs.

scholarly journals NAADP induces pH changes in the lumen of acidic Ca2+ stores

2007 ◽  
Vol 402 (2) ◽  
pp. 301-310 ◽  
Author(s):  
Anthony J. Morgan ◽  
Antony Galione
Keyword(s):  
Nicotinic Acid ◽  
Direct Effect ◽  
Sea Urchin ◽  
Cell Types ◽  
Receptor Activation ◽  
Fluorescence Measurements ◽  
Low Concentrations ◽  
Inositol 1,4,5 Trisphosphate ◽  
Intracellular Organelles ◽  
First Time

NAADP (nicotinic acid–adenine dinucleotide phosphate)-induced Ca2+ release has been proposed to occur selectively from acidic stores in several cell types, including sea urchin eggs. Using fluorescence measurements, we have investigated whether NAADP-induced Ca2+ release alters the pHL (luminal pH) within these acidic stores in egg homogenates and observed their prompt, concentration-dependent alkalinization by NAADP (but not β-NAD+ or NADP). Like Ca2+ release, the pHL change was desensitized by low concentrations of NAADP suggesting it was secondary to NAADP receptor activation. Moreover, this was a direct effect of NAADP upon the acidic stores and not secondary to increases in cytosolic Ca2+ as it was not mimicked by IP3 (inositol 1,4,5-trisphosphate), cADPR (cyclic adenine diphosphoribose), ionomycin, thapsigargin or by direct addition of Ca2+, and was not blocked by EGTA. The results of the present study further support acidic stores as targets for NAADP and for the first time reveal an adjunct role for NAADP in regulating the pHL of intracellular organelles.

A novel Ca2+-induced Ca2+ release mechanism mediated by neither inositol trisphosphate nor ryanodine receptors

2002 ◽  
Vol 361 (3) ◽  
pp. 605-611 ◽  
Author(s):  
Frank WISSING ◽  
Edmund P. NEROU ◽  
Colin W. TAYLOR
Keyword(s):  
Ryanodine Receptors ◽  
Ruthenium Red ◽  
Release Mechanism ◽  
Temperature Sensitive ◽  
Half Time ◽  
Ip3 Receptors ◽  
Inositol 1,4,5 Trisphosphate ◽  
Before And After ◽  
Partial Inactivation ◽  
Ca2 Channels

Members of both major families of intracellular Ca2+ channels, ryanodine and inositol 1,4,5-trisphosphate (IP3) receptors, are stimulated by substantial increases in cytosolic free Ca2+ concentration ([Ca2+]c). They thereby mediate Ca2+-induced Ca2+ release (CICR), which allows amplification and regenerative propagation of intracellular Ca2+ signals. In permeabilized hepatocytes, increasing [Ca2+]c to 10μM stimulated release of 30±1% of the intracellular stores within 60s; the EC50 occurred with a free [Ca2+] of 170±29nM. This CICR was abolished at 2°C. The same fraction of the stores was released by CICR before and after depletion of the IP3-sensitive stores, and CICR was not blocked by antagonists of IP3 receptors. Ryanodine, Ruthenium Red and tetracaine affected neither the Ca2+ content of the stores nor the CICR response. Sr2+ and Ba2+ (EC50 = 166nM and 28μM respectively) mimicked the effects of increased [Ca2+] on the intracellular stores, but Ni2+ blocked the passive leak of Ca2+ without blocking CICR. In rapid superfusion experiments, maximal concentrations of IP3 or Ca2+ stimulated Ca2+ release within 80ms. The response to IP3 was complete within 2s, but CICR continued for tens of seconds despite a slow [half-time (t1/2) = 3.54±0.07s] partial inactivation. CICR reversed rapidly (t1/2 = 529±17ms) and completely when the [Ca2+] was reduced. We conclude that hepatocytes express a novel temperature-sensitive, ATP-independent CICR mechanism that is reversibly activated by modest increases in [Ca2+], and does not require IP3 or ryanodine receptors or reversal of the sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase. This mechanism may both regulate the Ca2+ content of the intracellular stores of unstimulated cells and allow even small intracellular Ca2+ signals to be amplified by CICR.

scholarly journals Nicotinate-adenine dinucleotide phosphate-induced Ca2+-release does not behave as a Ca2+-induced Ca2+-release system

1996 ◽  
Vol 316 (3) ◽  
pp. 709-711 ◽  
Author(s):  
Eduardo N. CHINI ◽  
Thomas P. DOUSA
Keyword(s):  
Sea Urchin ◽  
The Other ◽  
Release Mechanism ◽  
Inositol 1 ◽  
Release System ◽  
Release Mechanisms ◽  
Sea Urchin Egg ◽  
Wide Range ◽  
Cyclic Adp Ribose ◽  
Regulatory Impact

We investigated the dependence of nicotinate–adenine dinucleotide phosphate (NAADP)-induced Ca2+ release from intracellular stores of sea urchin egg homogenates, upon extravesicular Ca2+. In contrast to the Ca2+ release induced by inositol 1´,4´,5´trisphosphate (IP3) or cyclic ADP-ribose (cADPR), the Ca2+ release induced by NAADP was completely independent of the free extravesicular Ca2+ over a wide range of concentrations (0–0.1 mM). The Ca2+ release triggered by either cADPR or IP3 was biphasically modulated by extravesicular Ca2+, and the Ca2+ release by these agents was abolished when the extravesicular Ca2+ was removed by chelation with 2 mM EGTA. On the other hand, NAADP-triggered Ca2+ release was not influenced by EGTA. These data indicate that while both cADPR and IP3 systems behave as functional Ca2+-induced Ca2+ release mechanisms, NAADP activates a Ca2+ release mechanism which is independent of the presence of extravesicular Ca2+. Therefore, the NAADP-sensitive Ca2+ release mechanisms may have a unique regulatory impact upon intracellular Ca2+ homoeostasis.

scholarly journals Differential regulation of nicotinic acid–adenine dinucleotide phosphate and cADP-ribose production by cAMP and cGMP

1998 ◽  
Vol 331 (3) ◽  
pp. 837-843 ◽  
Author(s):  
Heather L. WILSON ◽  
Antony GALIONE
Keyword(s):  
Nicotinic Acid ◽  
Sea Urchin ◽  
Calcium Release ◽  
Second Messengers ◽  
Differential Regulation ◽  
Sea Urchin Egg ◽  
Inositol 1,4,5 Trisphosphate ◽  
Extracellular Stimuli ◽  
Camp And Cgmp ◽  
Temperature Optima

The sea urchin egg has been used as a system to study calcium-release mechanisms induced by inositol 1,4,5-trisphosphate (IP3), cADP-ribose (cADPR), and more recently, nicotinic acid–adenine dinucleotide phosphate (NAADP). In order that cADPR and NAADP may be established as endogenous messengers for calcium release, the existence of intracellular enzymes capable of metabolizing these molecules must be demonstrated. In addition, intracellular levels of cADPR and NAADP should be under the control of extracellular stimuli. It has been shown that cGMP stimulates the synthesis of cADPR in the sea urchin egg. The present study shows that the sea urchin egg is capable of synthesizing and degrading NAADP. cADPR and NAADP synthetic activities appear to be separate, with different cellular localizations, pH and temperature optima. We suggest that in the sea urchin egg, cADPR and NAADP production may be differentially regulated by receptor-coupled second messengers, with cADPR production being regulated by cGMP and NAADP production modulated by cAMP.

Two ultrastructurally distinct tubulin paracrystals induced in sea-urchin eggs by vinblastine sulphate

1976 ◽  
Vol 20 (1) ◽  
pp. 79-89 ◽  
Author(s):  
D. Starling
Keyword(s):  
Sea Urchin ◽  
Binding Sites ◽  
Mammalian Cells ◽  
The Other ◽  
Sea Urchin Eggs ◽  
Vincristine Sulphate ◽  
Vinblastine Sulphate ◽  
Available Information ◽  
Tubulin Paracrystals

Two types of ultrastructurally distinct tubulin paracrystals have been induced in sea-urchin eggs with vinblastine sulphate (VLB) under different sets of conditions. One type of paracrystal appears to consist of hexagonally-close packed microtubules and closely resembles paracrystals present in mammalian cells treated with vinblastine or vincristine sulphate, but not previously reported in sea-urchin eggs. The other type is also made up of tubulin subunits, but these do not seem to have polymerized into microtubules. Both types of paracrystal are induced in sea-urchin eggs in the presence of VLB at a time when tubulin subunits would not normally polymerize. Possible mechanisms for tubulin activation and the induction of paracrystal formation are discussed in respect to the available information on the binding sites of the tubulin subunits.

Nicotinic acid–adenine dinucleotide phosphate (NAADP) elicits specific microsomal Ca2+ release from mammalian cells

2001 ◽  
Vol 353 (3) ◽  
pp. 531-536 ◽  
Author(s):  
Ahad N.-K. YUSUFI ◽  
Jingfei CHENG ◽  
Michael A. THOMPSON ◽  
Eduardo N. CHINI ◽  
Joseph P. GRANDE
Keyword(s):  
Nicotinic Acid ◽  
Intracellular Calcium ◽  
Sea Urchin ◽  
Mammalian Cells ◽  
Calcium Release ◽  
Cultured Cells ◽  
Mesangial Cells ◽  
Rat Kidney ◽  
Leukaemia Cell Line ◽  
Mammalian Tissues

Nicotinic acid–adenine dinucleotide phosphate (NAADP), a molecule derived from β-NADP, has been shown to promote intracellular calcium release in sea urchin eggs. However, there is little information regarding the role of NAADP in the regulation of intracellular calcium fluxes in mammalian cells. We found recently that several mammalian tissues have a high capacity for NAADP synthesis, as assessed by sea urchin egg bioassay. To determine the functional significance of NAADP production by mammalian tissues, we sought to determine whether NAADP is capable of inducing calcium release from microsomes prepared from cultured cells. We found that NAADP, but not β-NADP, activates a specific microsomal calcium release system in mesangial cells isolated from rat kidney; NAADP was without effect in renal tubular epithelial cells. NAADP-induced calcium release is not affected by inhibitors of the inositol 1,4,5-trisphosphate or ryanodine channels. However, NAADP-elicited calcium release was inhibited by L-type calcium channel blockers and by alkaline phosphatase treatment of NAADP. NAADP also promotes specific microsomal calcium release in rat vascular smooth muscle cells, cardiac myocytes, fibroblasts and a human leukaemia cell line, indicating that the capacity for NAADP-induced calcium release is widespread in mammalian cells. We propose that NAADP may be an important regulator of intracellular calcium in many mammalian tissues.

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