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Nicotinic Acid Adenine Dinucleotide Phosphate: A New Ca²⁺ Releasing Agent in Kidney

JINGFEI CHENG^*, AHAD N. K. YUSUFI^*, MICHAEL A. THOMPSON^*, EDUARDO N. CHINI and JOSEPH P. GRANDE^*

^* Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.

Correspondence to Dr. Joseph P. Grande, Department of Laboratory Medicine, Mayo Clinic and Foundation, Rochester, MN 55905. Phone: 507-284-6988; Fax: 507-284-3757; E-mail: grande.joseph{at}mayo.edu

	Abstract

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Abstract. Nicotinic acid adenine dinucleotide phosphate (NAADP), a molecule derived from ß-NADP, has been shown to trigger Ca²⁺ release from intracellular stores of invertebrate eggs and mammalian cell microsomes. NAADP-induced Ca²⁺ release occurs through a mechanism distinct from that of inositol-1,4,5-trisphosphate— or cyclic ADP-ribose—elicited Ca²⁺ release. This study investigated whether NAADP can be synthesized in rat kidney. Extracts from glomeruli, mesangial cells, and papilla have high NAADP synthetic capacities. Conversely, synthesis of NAADP in kidney cortex was almost undetectable. Furthermore, 9-cis-retinoic acid significantly up-regulated NAADP synthesis in mesangial cells. Authenticity of NAADP biosynthesis in glomeruli was affirmed by HPLC analysis. NAADP stimulated Ca²⁺ release from mesangial cell microsomes through a pathway distinct from that of inositol-1,4,5-trisphosphate or cyclic ADP-ribose. NAADP-triggered Ca²⁺ release may play an important role in regulation of renal function.

	Introduction

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Release of Ca²⁺ from intracellular stores is an important component of several signaling pathways (1,2). Two major mechanisms of intracellular Ca²⁺ release are well known: (1) the inositol-1,4,5,-trisphosphate (IP₃)-triggered Ca²⁺ release (1,2) and (2) the so-called Ca²⁺ -induced Ca²⁺ -release system, mediated by the ryanodine receptor/channel and activated by the endogenous nucleotide cyclic ADP-ribose (cADPR) (3,4,5,6,7). In addition to Ca²⁺ release induced by cADPR and IP₃, nicotinic acid adenine dinucleotide phosphate (NAADP) was recently characterized as a potent stimulator of intracellular Ca²⁺ release in invertebrates and mammalian cells (7,8,9,10,11,12,13,14,15). NAADP-induced Ca²⁺ release was first demonstrated in sea urchin eggs (7,8,9), where nanomolar concentrations trigger Ca²⁺ release via a mechanism that differs in many ways from cADPR and IP₃ (7,8,9,10,11,12,13,14,15).

cADPR is synthesized by the enzyme ADP-ribosyl-cyclase (ADPR-cyclase) (7). In mammalian tissues, the majority of the enzymatic activity is catalyzed by lymphocyte antigen CD38, also identified as CD38 ADPR-cyclase (16,17). Recently, we described that in kidney parenchyma and its components, only glomeruli are endowed with a high capacity for cADPR synthesis (18). Furthermore, we demonstrated that cADPR synthesis and Ca²⁺ release are present in renal mesangial cells (18,19). We have proposed that cADPR may play an important signaling role in this cell type (18,19).

In contrast with the metabolism of cADPR, far less is known about synthesis of NAADP in mammalian tissues. We previously showed that NAADP synthesis is present in several rat tissues, including brain, heart, liver, and spleen (20). However, we observed no detectable synthesis of NAADP in rat kidney (20). In view of the recent finding of NAADP-induced Ca²⁺ release in pancreatic acinar cells and brain microsomes (21,22), we investigated NAADP synthesis in extracts from major zones of rat kidney parenchyma as well as isolated glomeruli and mesangial cells. Here we report that in extracts of rat cortex, NAADP synthesis was almost undetectable. In contrast, high capacity synthesis of NAADP was found in glomeruli, mesangial cells, and papilla. This new insight provides important information about synthesis of NAADP in kidney parenchyma and reveals that glomeruli and renal papilla are endowed with a high capacity for NAADP synthesis. We suggest a role for NAADP signaling in regulation of renal function.

	Materials and Methods

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Tissues were harvested from adult male Sprague-Dawley rats (250 to 350 g body wt) and killed under cocktail anesthesia (50% xylazine, 20 mg/ml and 50% Ketalar, 100 mg/ml; 0.1 ml cocktail/100 g body wt). Kidney and liver were quickly dissected, chilled, and minced in ice-cold solution containing 0.25 M sucrose, 20 mM Tris-HCl (pH 7.2). Tissues were Dounce homogenized (1:4; wt/vol) using 8 to 10 strokes and centrifuged at 4000 x rpm for 10 min at 4°C. The supernatant, denoted further as extract, was collected and used for determination of enzymatic synthesis of NAADP. The protein content was measured by the method of Lowry et al. (23).

Preparation of Glomeruli
Glomeruli were prepared by sequential sieving as described previously (24). Briefly, rats were anesthetized by intraperitoneal injection of cocktail, and the kidneys were perfused (10 ml/min) in situ with prewarmed (37°C) Hanks balanced salt solution followed by ice-cold Hanks balanced salt solution. Cortical tissue was finely minced before passing through a stainless steel sieve (250-µm pore size). The resulting suspension was passed several times though a 22-gauge needle to ensure complete dispersion and sequentially sieved through nylon mesh of 390-, 250-, and 211-µm pore openings. The cortical suspension was then passed over a 60-µm sieve to collect the glomeruli. Purity of glomeruli was evaluated by microscopic examination, and counting preparations contained >95% glomeruli (24).

Synthesis of NAADP
NAADP was synthesized by incubating rat kidney homogenates (1 mg/ml) or membrane fraction of mesangial cells (0.3 mg/ml) with 0.2 mM ß-NADP, 7 mM nicotinic acid at 37°C, in a medium containing 0.25 M sucrose and 20 mM Tris HCI (pH 6.5) for 60 min, or as specified in the Results section. The content of NAADP was determined using a sea urchin egg homogenate Ca²⁺ release bioassay (7,25).

Sea Urchin Egg Homogenate Bioassay
Homogenates from sea urchin eggs (Lytechinus pictus) were prepared as described previously (7). Frozen homogenates were thawed in a 17°C water bath and diluted to 1.25% in a medium containing 2 u/ml creatine kinase, 4 mM phosphocreatine, 1 mM ATP, 3 µM fluo-3. Fluo-3 fluorescence was monitored at 490 nm excitation and 535 nm emission in a 250-µl cuvette at 17°C with a circulating water bath and continuously mixed with a magnetic stirring bar, using a spectrofluorometer (F-2000; Hitachi, Ltd., Tokyo, Japan) (7,25).

Mesangial Cells
Mesangial cells were grown in cell culture from glomeruli that were isolated from adult Sprague-Dawley rats by differential sieving (26). Cell outgrowths were characterized as mesangial cells by positive immunohistochemical staining for vimentin and smooth muscle-specific actin and by negative staining for cytokeratins, factor VIII-related antigen, and common leukocyte antigen. Mesangial cells were harvested and membrane fraction was prepared as described previously (27).

Preparation of NAADP
Authentic NAADP was synthesized from ß-NADP and nicotinic acid via the base-exchange enzymatic reaction catalyzed by brain NAD-glycohydrolase (7,28). The nucleotides were purified by anion-exchange HPLC (7). NAADP in all experiments was at least 97% pure as determined by HPLC analysis.

⁴⁵Ca²⁺ Release from Microsomes
Freshly prepared microsomes (approximately 100 µg of protein) were passively loaded by incubating for 3 h at room temperature (21°C) in a medium containing 100 mM NaCl, 25 mM HEPES (pH 7.2), 1 mM CaCl₂, and 1 µC of ⁴⁵Ca²⁺. Release of ⁴⁵Ca²⁺ from loaded microsomes was initiated by 10-fold dilution of microsomal suspension with a buffer containing 100 mM NaCl, 1 mM ethyleneglycol-bis(ß-aminoethyl ether)-N,N'-tetraacetic acid, 1 mM MgCl₂, and 25 mM HEPES (pH 7.2) (19). After 10 s, the suspension was further diluted in the same medium without or with 10 µM NAADP (final dilution 50-fold). ⁴⁵Ca²⁺ efflux was stopped 90 s after the second dilution by test agents, and the ⁴⁵Ca²⁺ retained in microsomes was separated from free ⁴⁵Ca²⁺ by a rapid filtration technique using Whatman GF/B filters. The filters were rinsed three times with a solution containing 100 mM NaCl, 1 mM ethyleneglycol-bis(ß-aminoethyl ether)-N,N'-tetraacetic acid, 4 mM MgCl₂, and 25 mM HEPES (pH 7.2). The ⁴⁵Ca²⁺ retained in microsomes was determined by liquid scintillation counting.

L. pictus was obtained from Marinus, Inc. (Long Beach, CA). Fluo-3 was purchased from Molecular Probes (Eugene, OR). All other reagents, of the highest purity grade available, were supplied by Sigma Co. (St. Louis, MO).

Statistical Analyses
When appropriate, results were evaluated statistically by t test.

	Results

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NAADP Synthesis in Kidney Parenchyma
We determined NAADP synthesis in extracts of renal cortex, medulla, and papilla. We found that papilla and, to a lesser extent, medulla were able to synthesize NAADP from ß-NADP and nicotinic acid (Figure 1). The rate of synthesis of NAADP in papilla is comparable to that observed in liver. In contrast, kidney cortex has a limited capacity for synthesis of NAADP (Figure 1). The amount of NAADP synthesized in cortex is near the lower limit of detection of the sea urchin egg homogenate bioassay (7). We also observed that with time the NAADP synthesized was hydrolyzed in kidney tissues more rapidly than in liver (Figure 1). This observation is compatible with our previous observation that rat kidney has a higher rate of NAADP hydrolysis than other tested tissues (20).

View larger version (17K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 1. Biosynthesis of nicotinic acid adenine dinucleotide phosphate (NAADP) by rat kidney homogenates. Rat kidney and liver homogenates (1 mg/ml) were incubated at 37°C in a medium containing 7 mM nicotinic acid, 0.2 mM ß-NADP, and 20 mM Tris HCl (pH 6.5) for 7 min, 15 min, 30 min, and 60 min. Aliquots (3 µl) of the assay media were tested for Ca2+ release activity using the sea urchin egg homogenate bioassay. NAADP content was determined from calibration curve of the sea urchin egg homogenate Ca2+ release bioassay. The calibration curve was generated by responses to known concentration of authentic purified NAADP standards. [UNK], liver; , papilla; , medulla; , cortex; , glomeruli.

Synthesis of NAADP in Glomeruli
In view of the fact that synthesis of other signaling molecules can be distinctly localized in specific segments of the nephron (29), we determined NAADP synthesis in extracts of isolated glomeruli. Unlike extracts of renal cortex, glomeruli have a high capacity for NAADP synthesis (Figure 1). We further characterized the NAADP synthesis in glomeruli. The synthesis of NAADP was highly dependent on the concentration of precursor molecules, including ß-NADP (Figure 2A) and nicotinic acid (Figure 2B). In addition, we observed a pH dependence for the synthesis of NAADP in glomeruli (Figure 3). Synthesis of NAADP in glomeruli is increased by acidification of the media; the optimal pH is approximately 4 (Figure 3). Similar pH dependence for synthesis of NAADP has been demonstrated in other systems, including sea urchin egg homogenates (25). Furthermore, the authenticity of NAADP generated by glomeruli was affirmed by HPLC analysis (Figure 4).

View larger version (10K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 2. Dose-dependence of ß-NADP and nicotinic acid on NAADP synthesis in rat kidney. (A) Dose-dependence of ß-NADP. Rat glomeruli homogenate (1 mg/ml) was incubated with 7 mM nicotinic acid and different concentrations of ß-NADP as substrates for 15 min, and the NAADP content was determined using the sea urchin egg homogenate bioassay. (B) Dose-dependence of nicotinic acid. Renal LLC-PK1 cell homogenate (1 mg/ml) was incubated with 0.2 mM ß-NADP and different concentrations of nicotinic acid for 15 min, and the NAADP content was determined by sea urchin egg homogenate bioassay.

View larger version (12K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 3. pH-dependence of NAADP production in rat glomeruli. Glomeruli homogenate (1 mg/ml) was incubated with 0.2 mM ß-NADP and 7 mM nicotinic acid in different pHs for 15 min. NAADP content was determined by sea urchin egg homogenate bioassay.

View larger version (13K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 4. HPLC determination of NAADP. Rat glomeruli homogenate (1 mg/ml) was incubated with 0.2 mM ß-NADP and 7 mM nicotinic acid in a 20 mM Tris HCl buffer (pH 4.0) at 37°C for 1 h. The reaction was stopped by addition of equal volume of cold acetone and centrifuged 2000 x g for 2 min. After acetone evaporation, the supernatant was subjected to anion-exchange HPLC analysis. The figure shows HPLC analysis of incubate at time 0 min ([UNK]) and 60 min ([UNK]) of incubation.

Synthesis of NAADP in Mesangial Cells
We further explored synthesis of NAADP in glomerular mesangial cells. We observed that mesangial cells showed a high capacity for synthesis of NAADP (Figure 5). In vascular smooth muscle cells and in LLC-PK1 cells, we previously showed that cADPR synthesis is induced by retinoic acid (27,30). Here we observed that incubation of mesangial cells with retinoic acid promotes a threefold increase in the initial rate of NAADP synthesis in these cells (Figure 5). This is the first described upregulation of NAADP synthesis in mammalian cells. We also observed a similar stimulation of NAADP synthesis by retinoic acid in LLC-PK1 and HL-60 cells (data not shown).

View larger version (16K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 5. Synthesis of NAADP in mesangial cells. Mesangial cells were incubated with ([UNK]) or without () 1 µM 9-cis retinoic acid for 24 h, and membrane fraction was prepared as described in the Materials and Methods section. Membrane fraction of mesangial cells (0.3 mg/ml) was incubated at 37°C with 0.2 mM ß-NADP and 7 mM nicotinic acid for 5 min, 10 min, 30 min, and 60 min. The amount of NAADP produced was measured by sea urchin egg homogenate Ca2+ release bioassay.

NAADP Induces Ca²⁺ Release from Mesangial Cell Microsomes
We also determined whether glomerular mesangial cells possess an NAADP-sensitive Ca²⁺ release mechanism. NAADP elicited Ca²⁺ release from rat mesangial cell microsomes in a dose-dependent manner, with maximal Ca²⁺ release observed after administration of 10 µM NAADP (Figure 6). Heparin, an IP₃ receptor antagonist, and 8-bromo-cADPR and ruthenium red, selective inhibitors of cADPR-mediated Ca²⁺ release through the ryanodine receptor/channel, had no effect on Ca²⁺ release activity triggered by NAADP (Figure 7). On the basis of these findings, it seems that NAADP promotes Ca²⁺ release from mesangial cell microsomes through a pathway functionally distinct from that of IP₃ or cADPR. The magnitude and time course of NAADP-induced Ca²⁺ release was similar to that of IP₃-mediated Ca²⁺ release in mesangial cell microsomes (Figure 8).

View larger version (11K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 6. Dose dependency of NAADP-induced 45Ca2+ release. Preloaded microsomes were incubated with different concentrations of NAADP, and 45Ca2+ release was measured as described in the Materials and Methods section.

View larger version (52K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 7. Effect of NAADP and inhibitors of ryanodine receptor/channel and inositol-1,4,5,-trisphosphate (IP3) receptor on 45Ca2+ release from preloaded microsomes. Ca2+ release was performed as described in the Materials and Methods section. , control, no additions; [UNK], 10 µM NAADP; [UNK], 10 µM NAADP with 20 µM 8-br-cADPR (ryanodine channel inhibitor); , 10 µM NAADP with 8 µM heparin (IP3 receptor blocker); [UNK], 10 µM NAADP with ruthenium red (RR; ryanodine channel inhibitor).

View larger version (12K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 8. Time courses of 45Ca2+ release induced by NAADP and IP3. Passively loaded microsomes were incubated with 10 µM NAADP ([UNK]) or 8 µM IP3 () for various time periods, and 45Ca2+ release was measured as described in the Materials and Methods section.

	Discussion

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It has been previously shown that NAADP is synthesized in mammalian tissues (20,25,27,30,31) and can trigger Ca²⁺ release from intracellular stores in invertebrate and vertebrate cells (7,8,9,21,22), suggesting that NAADP-induced Ca²⁺ release may be widespread and thus contribute to the complexity of intracellular Ca²⁺ signaling. We previously reported that some rat tissues, including brain, heart, liver, and spleen but not whole kidney, can synthesize NAADP (20). The results of the present study provide novel fundamental information regarding the metabolism of NAADP in kidney. We found that glomeruli and papilla showed a very high capacity for NAADP synthesis, which was comparable to that observed in liver (Figure 1). In contrast, considerably less NAADP synthesis was found in extracts from renal cortex (Figure 1). Because glomeruli constitute only 5% of renal cortical mass (32), the extremely low capacity for NAADP synthesis in cortex compared with glomeruli may be due to the great diversity of cell populations in kidney. We previously reported that although limited amounts of cADPR were formed in whole kidney cortical tissue, high activity of cADPR synthesis was found in isolated glomeruli (18).

Although the role of NAADP system in kidney papilla is not known, it is important to note that regulation of intracellular Ca²⁺ is an important component in signal transduction in inner medullary collecting duct (IMCD) cells from papilla. It was recently revealed in IMCD cells from rat papilla that Ca²⁺ dependence is a unique phenomenon for stimulation of sorbitol efflux during hypotonic shock (33). It has also been reported that during hypotonic shock, intracellular Ca²⁺ is transiently elevated in IMCD cells and the increase seems to involve an initial Ca²⁺ release from intracellular stores followed by a rapid Ca²⁺ influx from the extracellular medium (34). Although the role of the NAADP-Ca²⁺ releasing system in papilla is speculative, it should be further investigated.

With respect to the site of NAADP synthesis in glomeruli, we found that extracts from mesangial cells grown in primary culture showed a significant rate of NAADP synthesis (Figure 5). Mesangial cells are specialized pericytes in glomeruli and are essential for maintenance and regulation of glomerular function (35,36,37). Contractility and other functions of mesangial cells are mainly regulated by Ca²⁺ released from intracellular stores (35,36,37,38). Numerous stimuli modulate the function of mesangial cells by binding to requisite receptors in the plasma membrane and via the IP₃-Ca²⁺ release pathway (38). The presence of IP₃ receptors in mesangial cells has been documented (39). More recent, we confirmed that ryanodine receptor/channel are also expressed in mesangial cells by [³H]-ryanodine binding to microsomal fractions of mesangial cells and by Western blot analysis (19). In addition, we observed that the ⁴⁵Ca²⁺ release from preloaded mesangial cell microsomes was greatly stimulated by cADPR (19) and NAADP. These data suggest that in addition to the IP₃-Ca²⁺ release pathway, cADPR- and NAADP-induced Ca²⁺ release signaling pathways may regulate the function of mesangial cells.

This study also showed that kidney extracts have a higher rate of NAADP degradation than other rat tissues. Various phosphomonoesterases and phosphodiesterases may inactivate NAADP (20). Extraordinarily high inactivating activity of kidney extract may be due to high content and activity of alkaline phosphatase (40) and acid phosphatase (41) in proximal tubules.

It has been shown that the enzyme responsible for both cADPR and NAADP production has a marked pH dependence, favoring cADPR formation at a higher pH and NAADP formation at a lower pH (25). In our studies, we found that the maximal NAADP formation was observed at pH 4 (Figure 3). Although NAADP synthesis at pH 7 is relatively low compared with its synthesis at more acid pH, it was significantly higher than cADPR synthesis at pH 7 (7 nmol NAADP/mg protein per min compared with 0.13 nmol cADPR/mg protein per min) (18), thus indicating that although the optimal condition for NAADP synthesis is in the acidic cellular compartments, NAADP production can occur in the cytosol as well.

In conclusion, our results provide strong evidence that NAADP can be synthesized and inactivated in kidney and that NAADP formation is localized in glomeruli and papilla. Furthermore, we found that NAADP induces Ca²⁺ release from mesangial cell microsomes through a pathway that is functionally distinct from that of IP₃ or cADPR. We provide preliminary evidence that NAADP production may be stimulated by extracellular stimuli, retinoic acid in particular. These data together suggest that the NAADP-Ca²⁺ release system may play a role in regulation of renal function. Future studies to determine mechanisms that underlie NAADP production will define the role of this calcium signaling system in renal pathophysiologic states.

	Acknowledgments

 
This research was supported in part by the American Heart Association (Minnesota affiliate), Grant-in-Aid to E.N.C., NIH Grants DK-30597 and DK-16105, and by Mayo Foundation. The authors thank Henry Walker and Dr. Claudia C. S. Chini for critical reading of the manuscript. The excellent secretarial assistance of Cherish Grabau is appreciated.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Berridge MJ: The biology and medicine of calcium signaling. Mol Cell Endocrinol 98:119 -124, 1994[Medline]
2. Clapham DE: Calcium signaling. Cell80 : 259-268,1995[Medline]
3. Coranado R, Morrissette J, Sukhareva M, Vaughan DM: Structure and function of ryanodine receptors. Am J Physiol266 : C1485-C1504,1994[Abstract/Free Full Text]
4. Lee HC: Cyclic ADP-ribose: A calcium mobilizing metabolite of NAD⁺. Mol Cell Biochem138 : 229-235,1994[Medline]
5. Galione A, White A: Ca²⁺ release induced by cyclic ADP-ribose. Trends Cell Biol 4:431 -436, 1994[Medline]
6. Dousa TP, Chini EN, Beers KW: Adenine nucleotide diphosphates: Emerging second messengers acting via intracellular Ca²⁺ release. Am J Physiol 271:C1007 -C1024, 1996[Abstract/Free Full Text]
7. Chini EN, Beers KW, Dousa TP: Nicotinate adenine dinucleotide phosphate (NAADP) triggers a specific calcium release system in sea urchin eggs. J Biol Chem 270:3216 -3223, 1995[Abstract/Free Full Text]
8. Lee HC, Aarhus RA: A derivative of NADP mobilizes Ca²⁺ stores insensitive to inositol triphosphate and cyclic ADP-ribose. J Biol Chem 270:2152 -2157, 1995[Abstract/Free Full Text]
9. Chini EN, Beers KW, Chini CS, Dousa TP: Specific modulation of cyclic ADP-ribose-induced Ca²⁺ release by polyamines. Am J Physiol 269:C1042 -C1047, 1995[Abstract/Free Full Text]
10. Perez-Terzic CM, Chini EN, Shen SS, Dousa TP, Clapham DE: Ca²⁺ release triggered by nicotinate adenine dinucleotide phosphate in intact sea urchin eggs. Biochem J312 : 955-959,1995
11. Chini EN, Dousa TP: Nicotinate adenine dinucleotide phosphate-induced Ca²⁺ release does not behave as a Ca²⁺ -induced Ca²⁺ - release system. Biochem J316 : 709-711,1996
12. Chini EN, Liang M, Dousa TP: Differential effect of pH upon cyclic-ADP-ribose and nicotinate adenine dinucleotide phosphate-induced Ca²⁺ release system. Biochem J335 : 499-504,1998
13. Genazzani AA, Galione A: Nicotinic acid adenine dinucleotide phosphate mobilizes Ca²⁺ from a thapsigargin-insensitive pool. Biochem J 315:721 -725, 1996
14. Genazzani AA, Galione A: A Ca²⁺ release mechanism gated by the novel pyridine nucleotide NAADP. Trends Pharmacol Sci 18: 108-110,1997[Medline]
15. Graeff RM, Podein RJ, Aarhus R, Lee HC: Magnesium ions but not ATP inhibit cyclic ADP-ribose-induced Ca²⁺ -release. Biochem Biophys Res Commun 206:786 -791, 1995[Medline]
16. Howard M, Grimaldi JC, Brazan JF, Lund FE: Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38. Science 262:1056 -1059, 1993[Abstract/Free Full Text]
17. Kukimoto I, Hoshino S, Kontani K, Inageda K, Nishina H, Takahashi K, Katada T: Stimulation of ADP-ribosyl cyclase activity of the cell surface antigen CD38 by zinc ions resulting from inhibition of its NAD⁺ glycohydrolase activity. Eur J Biochem239 : 177-182,1996[Medline]
18. Chini EN, Klener P Jr, Beers KW, Chini CS, Grande JP, Dousa TP: Cyclic ADP-ribose metabolism in rat kidney: High capacity for synthesis in glomeruli. Kidney Int 51:1500 -1506, 1997[Medline]
19. Yusufi ANK, Thompson MA, Walker HJ, Dousa TP: Ryanodine receptor/channel (RyR) for Ca²⁺ release in rat mesangial cells (MC) [Abstract]. J Am Soc Nephrol10 : 486A,1999
20. Chini EN, Dousa TP: Enzymatic synthesis and degradation of nicotinate adenine dinucleotide phosphate (NAADP), a Ca²⁺ - releasing agonist, in rat tissue. Biochem Biophys Res Commun 209:167 -174, 1995[Medline]
21. Cancela JM, Churchill GC, Galione A: Coordination of agonist-induced Ca²⁺ -signaling patterns by NAADP in pancreatic acinar cells. Nature 398:74 -76, 1999[Medline]
22. Bak J, White P, Timar G, Missiaen L, Genazzani AA, Galione A: Nicotinic acid adenine dinucleotide phosphate triggers Ca²⁺ release from brain microsomes. Curr Biol9 : 751-754,1999[Medline]
23. Lowry OH, Rosebrogh NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem193 : 265-275,1951[Free Full Text]
24. Chini CS, Chini EN, Williams JM, Matousovic K, Dousa TP: Formation of reactive oxygen metabolites in glomeruli is suppressed by inhibition of cAMP phosphodiesterase isozyme type-IV. Kidney Int46 : 28-36,1994[Medline]
25. Aarhus R, Graeff RM, Dickey DM., Walseth TF, Lee HC: ADP-ribosyl cyclase and CD38 catalyze the synthesis of a calcium mobilizing metabolite from NADP⁺. J Biol Chem270 : 30327-30333,1995[Abstract/Free Full Text]
26. Matousovic K, Grande JP, Chini CS, Chini EN, Dousa TP: Inhibitors of cyclic nucleotide phosphodiesterase isozymes type-III and type-IV suppress proliferation of rat mesangial cells. J Clin Invest96 : 401-410,1995
27. Beers KW, Chini EN, Dousa TP: All-trans-retinoic acid stimulate synthesis of cyclic ADP-ribose in renal LLC-PK₁ cells. J Clin Invest 95:2385 -2390, 1995
28. Bernofsky C: Nicotinic acid adenine dinucleotide phosphate (NAADP⁺). Methods Enzymol66 : 105-112,1980[Medline]
29. Morel F, Doucet A: Hormonal control of kidney functions at the cell level. Physiol Rev 66:377 -468, 1986[Free Full Text]
30. De Toledo FGS, Cheng J, Dousa TP: Retinoic acid and triiodothyronine stimulate ADP-ribosyl cyclase activity in rat vascular smooth muscle cells. Biochem Biophys Res Commun238 : 847-850,1997[Medline]
31. Liang M, Chini EN, Cheng J, Dousa TP: Synthesis of NAADP and cADPR in mitochondria. Arch Biochem Biophys371 : 317-325,1999[Medline]
32. Pfaller W, Rittinger M: Quantitative morphology of the rat kidney. Int J Biochem 12:17 -22, 1980[Medline]
33. Bevan C, Theiß C, Kinne RKH: Roles of Ca²⁺ in sorbitol release from rat inner medullary collecting duct (IMCD) cells under hypoosmotic stress. Biochem Biophys Res Commun170 : 563-568,1990[Medline]
34. Mooren FC, Kinne RKH: Intracellular calcium in primary cultures of rat renal inner medullary collecting duct cells during variations of extracellular osmolality. Pflügers Arch 427:463 -472, 1994[Medline]
35. Bonventre JV: Calcium and calcium-related signaling pathways in glomerular mesangial cells. Clin Exper Pharmacol Physiol 23:65 -70, 1996[Medline]
36. Stockand JD, Sansom SC: Glomerular mesangial cells: Electrophysiology and regulation of contraction. Physiol Rev 78: 723-744,1998[Abstract/Free Full Text]
37. Schlondorff D: Roles of the mesangium in glomerular function. Kidney Int 49:1583 -1585, 1996[Medline]
38. Ardaillou R, Ronco P, Rondeau E: Biology of renal cells in culture. In: The Kidney, 5th Ed., edited by Brenner BM, Philadelphia, W.B. Saunders, 1996, pp99 -192
39. Monkawa T, Hayashi M, Miyawaki A, Sukiyama T, Yamamoto-Hino M, Hasegawa M, Furuichi T, Mikoshiba K, Saruta T: Localization of inositol 1,4,5-trisphosphate receptors in the rat kidney. Kidney Int 53: 296-301,1998[Medline]
40. Kempson SA, Kim JK, Northrup TE, Knox FG, Dousa TP: Alkaline phosphatase in adaptation to low dietary phosphate intake. Am J Physiol 237:E465 -E473, 1979
41. Le Hir ML, Dubach UC: Distribution of acid hydrolases in the nephron of normal and diabetic rats. Int J Biochem12 : 41-45,1980[Medline]

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