Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 2001 Feb 1;353(Pt 3):531–536. doi: 10.1042/0264-6021:3530531

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

A N Yusufi 1, J Cheng 1, M A Thompson 1, E N Chini 1, J P Grande 1
PMCID: PMC1221598  PMID: 11171049

Abstract

Nicotinic acid-adenine dinucleotide phosphate (NAADP), a molecule derived from beta-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 beta-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.

Full Text

The Full Text of this article is available as a PDF (141.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aarhus R., Dickey D. M., Graeff R. M., Gee K. R., Walseth T. F., Lee H. C. Activation and inactivation of Ca2+ release by NAADP+. J Biol Chem. 1996 Apr 12;271(15):8513–8516. doi: 10.1074/jbc.271.15.8513. [DOI] [PubMed] [Google Scholar]
  2. Aarhus R., Graeff R. M., Dickey D. M., Walseth T. F., Lee H. C. ADP-ribosyl cyclase and CD38 catalyze the synthesis of a calcium-mobilizing metabolite from NADP. J Biol Chem. 1995 Dec 22;270(51):30327–30333. doi: 10.1074/jbc.270.51.30327. [DOI] [PubMed] [Google Scholar]
  3. Bak J., White P., Timár G., Missiaen L., Genazzani A. A., Galione A. Nicotinic acid adenine dinucleotide phosphate triggers Ca2+ release from brain microsomes. Curr Biol. 1999 Jul 15;9(14):751–754. doi: 10.1016/s0960-9822(99)80335-2. [DOI] [PubMed] [Google Scholar]
  4. Bassols A., Massagué J. Transforming growth factor beta regulates the expression and structure of extracellular matrix chondroitin/dermatan sulfate proteoglycans. J Biol Chem. 1988 Feb 25;263(6):3039–3045. [PubMed] [Google Scholar]
  5. Berridge M. J. Elementary and global aspects of calcium signalling. J Physiol. 1997 Mar 1;499(Pt 2):291–306. doi: 10.1113/jphysiol.1997.sp021927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berridge M. J. Inositol trisphosphate and calcium signaling. Ann N Y Acad Sci. 1995 Sep 7;766:31–43. doi: 10.1111/j.1749-6632.1995.tb26646.x. [DOI] [PubMed] [Google Scholar]
  7. Berridge M. J. The biology and medicine of calcium signalling. Mol Cell Endocrinol. 1994 Jan;98(2):119–124. doi: 10.1016/0303-7207(94)90129-5. [DOI] [PubMed] [Google Scholar]
  8. Cancela J. M., Churchill G. C., Galione A. Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells. Nature. 1999 Mar 4;398(6722):74–76. doi: 10.1038/18032. [DOI] [PubMed] [Google Scholar]
  9. Cheng J., Yusufi A. N., Thompson M. A., Chini E. N., Grande J. P. Nicotinic acid adenine dinucleotide phosphate: a new Ca2+ releasing agent in kidney. J Am Soc Nephrol. 2001 Jan;12(1):54–60. doi: 10.1681/ASN.V12154. [DOI] [PubMed] [Google Scholar]
  10. Chini E. N., Beers K. W., Chini C. C., Dousa T. P. Specific modulation of cyclic ADP-ribose-induced Ca2+ release by polyamines. Am J Physiol. 1995 Oct;269(4 Pt 1):C1042–C1047. doi: 10.1152/ajpcell.1995.269.4.C1042. [DOI] [PubMed] [Google Scholar]
  11. Chini E. N., Beers K. W., Dousa T. P. Nicotinate adenine dinucleotide phosphate (NAADP) triggers a specific calcium release system in sea urchin eggs. J Biol Chem. 1995 Feb 17;270(7):3216–3223. doi: 10.1074/jbc.270.7.3216. [DOI] [PubMed] [Google Scholar]
  12. Chini E. N., Chini C. C., Bolliger C., Jougasaki M., Grande J. P., Burnett J. C., Jr, Dousa T. P. Cytoprotective effects of adrenomedullin in glomerular cell injury: central role of cAMP signaling pathway. Kidney Int. 1997 Oct;52(4):917–925. doi: 10.1038/ki.1997.413. [DOI] [PubMed] [Google Scholar]
  13. Chini E. N., Dousa T. P. Enzymatic synthesis and degradation of nicotinate adenine dinucleotide phosphate (NAADP), a Ca(2+)-releasing agonist, in rat tissues. Biochem Biophys Res Commun. 1995 Apr 6;209(1):167–174. doi: 10.1006/bbrc.1995.1485. [DOI] [PubMed] [Google Scholar]
  14. Chini E. N., Dousa T. P. Nicotinate-adenine dinucleotide phosphate-induced Ca(2+)-release does not behave as a Ca(2+)-induced Ca(2+)-release system. Biochem J. 1996 Jun 15;316(Pt 3):709–711. doi: 10.1042/bj3160709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chini E. N., Klener P., Jr, Beers K. W., Chini C. C., Grande J. P., Dousa T. P. Cyclic ADP-ribose metabolism in rat kidney: high capacity for synthesis in glomeruli. Kidney Int. 1997 May;51(5):1500–1506. doi: 10.1038/ki.1997.206. [DOI] [PubMed] [Google Scholar]
  16. Chini E. N., Liang M., Dousa T. P. Differential effect of pH upon cyclic-ADP-ribose and nicotinate-adenine dinucleotide phosphate-induced Ca2+ release systems. Biochem J. 1998 Nov 1;335(Pt 3):499–504. doi: 10.1042/bj3350499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Clapham D. E. Calcium signaling. Cell. 1995 Jan 27;80(2):259–268. doi: 10.1016/0092-8674(95)90408-5. [DOI] [PubMed] [Google Scholar]
  18. DiJulio D. H., Watson E. L., Pessah I. N., Jacobson K. L., Ott S. M., Buck E. D., Singh J. C. Ryanodine receptor type III (Ry3R) identification in mouse parotid acini. Properties and modulation of [3H]ryanodine-binding sites. J Biol Chem. 1997 Jun 20;272(25):15687–15696. doi: 10.1074/jbc.272.25.15687. [DOI] [PubMed] [Google Scholar]
  19. Dousa T. P., Chini E. N., Beers K. W. Adenine nucleotide diphosphates: emerging second messengers acting via intracellular Ca2+ release. Am J Physiol. 1996 Oct;271(4 Pt 1):C1007–C1024. doi: 10.1152/ajpcell.1996.271.4.C1007. [DOI] [PubMed] [Google Scholar]
  20. Galione A., White A. Ca2+ release induced by cyclic ADP-ribose. Trends Cell Biol. 1994 Dec;4(12):431–436. doi: 10.1016/0962-8924(94)90104-x. [DOI] [PubMed] [Google Scholar]
  21. Genazzani A. A., Empson R. M., Galione A. Unique inactivation properties of NAADP-sensitive Ca2+ release. J Biol Chem. 1996 May 17;271(20):11599–11602. doi: 10.1074/jbc.271.20.11599. [DOI] [PubMed] [Google Scholar]
  22. Genazzani A. A., Galione A. A Ca2+ release mechanism gated by the novel pyridine nucleotide, NAADP. Trends Pharmacol Sci. 1997 Apr;18(4):108–110. doi: 10.1016/s0165-6147(96)01036-x. [DOI] [PubMed] [Google Scholar]
  23. Genazzani A. A., Mezna M., Dickey D. M., Michelangeli F., Walseth T. F., Galione A. Pharmacological properties of the Ca2+-release mechanism sensitive to NAADP in the sea urchin egg. Br J Pharmacol. 1997 Aug;121(7):1489–1495. doi: 10.1038/sj.bjp.0701295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Herrmann-Frank A., Richter M., Sarközi S., Mohr U., Lehmann-Horn F. 4-Chloro-m-cresol, a potent and specific activator of the skeletal muscle ryanodine receptor. Biochim Biophys Acta. 1996 Feb 9;1289(1):31–40. doi: 10.1016/0304-4165(95)00131-x. [DOI] [PubMed] [Google Scholar]
  25. Hotchkiss R. S., Karl I. E. Calcium: a regulator of the inflammatory response in endotoxemia and sepsis. New Horiz. 1996 Feb;4(1):58–71. [PubMed] [Google Scholar]
  26. Hull R. N., Cherry W. R., Weaver G. W. The origin and characteristics of a pig kidney cell strain, LLC-PK. In Vitro. 1976 Oct;12(10):670–677. doi: 10.1007/BF02797469. [DOI] [PubMed] [Google Scholar]
  27. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  28. Lee H. C., Aarhus R. A derivative of NADP mobilizes calcium stores insensitive to inositol trisphosphate and cyclic ADP-ribose. J Biol Chem. 1995 Feb 3;270(5):2152–2157. doi: 10.1074/jbc.270.5.2152. [DOI] [PubMed] [Google Scholar]
  29. Lee H. C. Cyclic ADP-ribose: a calcium mobilizing metabolite of NAD+. Mol Cell Biochem. 1994 Sep;138(1-2):229–235. doi: 10.1007/BF00928466. [DOI] [PubMed] [Google Scholar]
  30. Lee H. C. Mechanisms of calcium signaling by cyclic ADP-ribose and NAADP. Physiol Rev. 1997 Oct;77(4):1133–1164. doi: 10.1152/physrev.1997.77.4.1133. [DOI] [PubMed] [Google Scholar]
  31. Liang M., Chini E. N., Cheng J., Dousa T. P. Synthesis of NAADP and cADPR in mitochondria. Arch Biochem Biophys. 1999 Nov 15;371(2):317–325. doi: 10.1006/abbi.1999.1463. [DOI] [PubMed] [Google Scholar]
  32. Mackrill J. J., Challiss R. A., O'connell D. A., Lai F. A., Nahorski S. R. Differential expression and regulation of ryanodine receptor and myo-inositol 1,4,5-trisphosphate receptor Ca2+ release channels in mammalian tissues and cell lines. Biochem J. 1997 Oct 1;327(Pt 1):251–258. doi: 10.1042/bj3270251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Matousovic K., Grande J. P., Chini C. C., Chini E. N., Dousa T. P. Inhibitors of cyclic nucleotide phosphodiesterase isozymes type-III and type-IV suppress mitogenesis of rat mesangial cells. J Clin Invest. 1995 Jul;96(1):401–410. doi: 10.1172/JCI118049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Richter M., Schleithoff L., Deufel T., Lehmann-Horn F., Herrmann-Frank A. Functional characterization of a distinct ryanodine receptor mutation in human malignant hyperthermia-susceptible muscle. J Biol Chem. 1997 Feb 21;272(8):5256–5260. doi: 10.1074/jbc.272.8.5256. [DOI] [PubMed] [Google Scholar]
  35. Sica A., Wang J. M., Colotta F., Dejana E., Mantovani A., Oppenheim J. J., Larsen C. G., Zachariae C. O., Matsushima K. Monocyte chemotactic and activating factor gene expression induced in endothelial cells by IL-1 and tumor necrosis factor. J Immunol. 1990 Apr 15;144(8):3034–3038. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES