Advertisement

Amino Acids

, Volume 46, Issue 8, pp 1805–1818 | Cite as

Current knowledge of d-aspartate in glandular tissues

  • Maria Maddalena Di FioreEmail author
  • Alessandra Santillo
  • Gabriella Chieffi Baccari
Invited Review

Abstract

Free d-aspartate (d-Asp) occurs in substantial amounts in glandular tissues. This paper reviews the existing work on d-Asp in vertebrate exocrine and endocrine glands, with emphasis on functional roles. Endogenous d-Asp was detected in salivary glands. High d-Asp levels in the parotid gland during development suggest an involvement of the amino acid in the regulation of early developmental phases and/or differentiation processes. d-Asp has a prominent role in the Harderian gland, where it elicits exocrine secretion through activation of the ERK1/2 pathway. Interestingly, the increase in NOS activity associated with d-Asp administration in the Harderian gland suggests a potential capability of d-Asp to induce vasodilatation. In mammals, an increase in local concentrations of d-Asp facilitates the secretion of anterior pituitary hormones, i.e., PRL, LH and GH, whereas it inhibits the secretion of POMC/α-MSH from the intermediate pituitary and of oxytocin from the posterior pituitary. d-Asp also acts as a negative regulator for melatonin synthesis in the pineal gland. Further, d-Asp can stereo-specifically modulate the production of sex steroids, thus taking part in the endocrine control of reproductive activity. Although d-Asp receptors remain to be characterized, gene expression of NR1 and NR2 subunits of NMDAr responds to d-Asp in the testis.

Keywords

d-Aspartate Salivary glands Harderian gland Endocrine glands d-Aspartate oxidase Aspartate racemase 

Notes

Conflict of interest

The authors declare no conflict of interest.

References

  1. Assisi L, Botte V, D’Aniello A, Di Fiore MM (2001) Enhancement of aromatase activity by d-aspartic acid in the ovary of the lizard Podarcis s. sicula. Reproduction 121(5):803–808PubMedCrossRefGoogle Scholar
  2. Boni R, Santillo R, Macchia G, Spinelli P, Ferrandino G, D’Aniello A (2006) d-Aspartate and reproductive activity in sheep. Theriogenology 65(7):1265–1278PubMedCrossRefGoogle Scholar
  3. Burrone L, Di Giovanni M, Di Fiore MM, Baccari GC, Santillo A (2010) Effects of d-aspartate treatment on d-aspartate oxidase, superoxide dismutase, and caspase 3 activities in frog (Rana esculenta) tissues. Chem Biodivers 7(6):1459–1466PubMedCrossRefGoogle Scholar
  4. Burrone L, Santillo A, Pinelli C, Baccari GC, Di Fiore MM (2012a) Induced synthesis of P450 aromatase and 17β-estradiol by d-aspartate in frog brain. J Exp Biol 215(Pt 20):3559–3565PubMedCrossRefGoogle Scholar
  5. Burrone L, Raucci F, Di Fiore MM (2012b) Steroidogenic gene expression following d-aspartate treatment in frog testis. Gen Comp Endocrinol 175(1):109–117PubMedCrossRefGoogle Scholar
  6. Chandrashekar KN, Muralidhara (2010) d-Aspartic acid induced oxidative stress and mitochondrial dysfunctions in testis of prepubertal rats. Amino Acids 38:817–827PubMedCrossRefGoogle Scholar
  7. Chieffi Baccari G, Minucci S, Di Matteo L, Chieffi G (1990) Harderian gland and the lacrimal gland of the lizard Podarcis s. sicula: histology, histochemistry, and ultrastructure. Anat Rec 226(3):269–278CrossRefGoogle Scholar
  8. Chieffi Baccari G, Marmorino C, Minucci S, Di Matteo L, Varriale B, d’Istria M, Chieffi G (1992) Mallory stain may indicate differential rates of RNA synthesis: I. A seasonal cycle in the harderian gland of the green frog (Rana esculenta). Eur J Histochem 36(1):81–90PubMedGoogle Scholar
  9. Chieffi Baccari G, Monteforte R, de Lange P, Raucci F, Farina P, Lanni A (2004) Thyroid hormone affects secretory activity and uncoupling protein-3 expression in rat harderian gland. Endocrinology 145:3338–3345PubMedCrossRefGoogle Scholar
  10. Chieffi G, Chieffi Baccari G, Di Matteo L, d’Istria M, Minucci S, Varriale B (1996) Cell biology of harderian gland. Int Rev Cytol 168:1–80PubMedCrossRefGoogle Scholar
  11. D’Aniello A, Giuditta A (1977) Identification of d-aspartic acid in the brain of Octopus vulgaris Lam. J Neurochem 29(6):1053–1057PubMedCrossRefGoogle Scholar
  12. D’Aniello A, Di Fiore MM, Fisher GH, Milone A, Seleni A, D’Aniello S, Perna AF, Ingrosso D (2000a) Occurrence of d-aspartic acid and N-methyl-d-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release. FASEB J 14:699–714PubMedGoogle Scholar
  13. D’Aniello G, Tolino A, D’Aniello A, Errico F, Fisher GH, Di Fiore MM (2000b) The role of d-aspartic acid and N-methyl-d-aspartic acid in the regulation of prolactin release. Endocrinology 141:3862–3870PubMedGoogle Scholar
  14. D’Aniello G, Ronsini S, Notari T, Grieco N, Infante V, D’Angelo N, Mascia F, Di Fiore MM, Fisher G, D’Aniello A (2012) d-Aspartate, a key element for the improvement of sperm quality. Adv Sex Med 2:47–53Google Scholar
  15. D’Aniello A (2007) d-Aspartic acid: an endogenous amino acid with an important neuroendocrine role. Brain Res Rev 53(2):215–234PubMedCrossRefGoogle Scholar
  16. D’Aniello A, Di Cosmo A, Di Cristo C, Annunziato L, Petrucelli L, Fisher G (1996) Involvement of d-aspartic acid in the synthesis of testosterone in rat testes. Life Sci 59:97–104PubMedCrossRefGoogle Scholar
  17. D’Aniello A, Di Fiore MM, D’Aniello G, Colin FE, Lewis G, Setchell BP (1998) Secretion of d-aspartic acid by the rat testis and its role in endocrinology of the testis and spermatogenesis. FEBS Lett 436(1):23–27PubMedCrossRefGoogle Scholar
  18. D’Aniello A, Spinelli P, De Simone A, D’Aniello S, Branno M, Aniello F, Fisher GH, Di Fiore MM, Rastogi RK (2003) Occurrence and neuroendocrine role of d-aspartic acid and N-methyl-d-aspartic acid in Ciona intestinalis. FEBS Lett 552:193–198PubMedCrossRefGoogle Scholar
  19. D’Aniello G, Ronsini S, Guida F, Spinelli P, D’Aniello A (2005) Occurrence of d-aspartic acid in human seminal plasma and spermatozoa: possible role in reproduction. Fertil Steril 84(5):1444–1449PubMedCrossRefGoogle Scholar
  20. D’Aniello G, Grieco N, Di Filippo MA, Cappiello F, Topo E, D’Aniello E, Ronsini S (2007) Reproductive implication of d-aspartic acid in human pre-ovulatory follicular fluid. Hum Reprod 22(12):3178–3183PubMedCrossRefGoogle Scholar
  21. Di Fiore MM, Assisi L, Botte V, D’Aniello A (1998) d-Aspartic acid is implicated in the control of testosterone production by the vertebrate gonad. Studies on the female green frog, Rana esculenta. J Endocrinol 157(2):199–207PubMedCrossRefGoogle Scholar
  22. Di Fiore MM, Lamanna C, Assisi L, Botte V (2008) Opposing effects of d-aspartic acid and nitric oxide on tuning of testosterone production in mallard testis during the reproductive cycle. Reprod Biol Endocrinol 6:28PubMedCentralPubMedCrossRefGoogle Scholar
  23. Di Giovanni M, Burrone L, Chieffi Baccari G, Topo E, Santillo A (2010a) Distribution of free d-aspartic acid and d-aspartate oxidase in frog Rana esculenta tissues. J Exp Zool A Ecol Genet Physiol 313(3):137–143PubMedGoogle Scholar
  24. Di Giovanni M, Topo E, Santillo A, D’Aniello A, Chieffi Baccari G (2010b) d-Aspartate binding sites in rat Harderian gland. Amino Acids 38(1):229–235PubMedCrossRefGoogle Scholar
  25. Di Matteo L, Minucci S, Chieffi Baccari G, Pellicciari C, d’Istria M, Chieffi G (1989) The harderian gland of the frog, Rana esculenta, during the annual cycle: histology, histochemistry and ultrastructure. Basic Appl Histochem 33(2):93–112PubMedGoogle Scholar
  26. Dunlop DS, Neidle A, McHale D, Dunlop DM, Lajtha A (1986) The presence of free d-aspartic acid in rodents and man. Biochem Biophys Res Commun 141(1):27–32PubMedCrossRefGoogle Scholar
  27. Errico F, Napolitano F, Nisticò R, Usiello A (2012) New insights on the role of free d-aspartate in the mammalian brain. Amino Acids 43(5):1861–1871PubMedCrossRefGoogle Scholar
  28. Furuchi T, Homma H (2005) Free d-aspartate in mammals. Biol Pharm Bull 28(9):1566–1570PubMedCrossRefGoogle Scholar
  29. Grant AC, Thomson J, Zammit VA, Shennan DB (2000) Volume-sensitive amino acid efflux from a pancreatic beta-cell line. Mol Cell Endocrinol 162(1–2):203–210PubMedGoogle Scholar
  30. Hadley ME, Haskell-Luevano C (1999) The proopiomelanocortin system. Ann NY Acad Sci 885:1–21PubMedCrossRefGoogle Scholar
  31. Hamase K, Homma H, Takigawa Y, Fukushima T, Santa T, Imai K (1997) Regional distribution and postnatal changes of D-amino acids in rat brain. Biochimica et Biophysica Acta 1334:214–222PubMedCrossRefGoogle Scholar
  32. Han H, Miyoshi Y, Ueno K, Okamura C, Tojo Y, Mita M, Lindner W, Zaitsu K, Hamase K (2011a) Simultaneous determination of d-aspartic acid and d-glutamic acid in rat tissues and physiological fluids using a multi-loop two-dimensional HPLC procedure. J Chromatogr B 879:3196–3202CrossRefGoogle Scholar
  33. Han H, Miyoshi Y, Oyama T, Konishi R, Mita M, Hamase K (2011b) Enantioselective micro-2D-HPLC determination of aspartic acid in the pineal glands of rodents with various melatonin contents. J Sep Sci 34:2847–2853PubMedCrossRefGoogle Scholar
  34. Hashimoto A, Nishikawa T, Oka T, Hayashi T, Takahashi K (1993) Widespread distribution of free d-aspartate in rat periphery. FEBS Lett 331(1–2):4–8PubMedCrossRefGoogle Scholar
  35. Hashimoto A, Oka T, Nishikawa T (1995) Anatomical distribution and postnatal changes in endogenous free d-aspartate and d-serine in rat brain and periphery. Eur J Neurosci 7:1657–1663PubMedCrossRefGoogle Scholar
  36. Hiasa M, Moriyama Y (2006) Immunohistochemical localization of d-aspartate in islets of Langerhans. Biol Pharm Bull 29(6):1251–1253PubMedCrossRefGoogle Scholar
  37. Homma H (2007) Biochemistry of d-aspartate in mammalian cells. Amino Acids 32(1):3–11PubMedCrossRefGoogle Scholar
  38. Huang AS, Beigneux A, Weil ZM, Kim PM, Molliver ME, Blackshaw S, Nelson RJ, Young SG, Snyder SH (2006) d-aspartate regulates melanocortin formation and function: behavioral alterations in d-aspartate oxidase-deficient mice. J Neurosci 26(10):2814–2819PubMedCrossRefGoogle Scholar
  39. Iharada M, Hiasa M, Kobara A, Moriyama Y (2007) Exocytosis of d-aspartate from INS-1E clonal beta cells. Biol Pharm Bull 30(7):1329–1331PubMedCrossRefGoogle Scholar
  40. Imai K, Fukushima T, Hagiwara K, Santa T (1995) Occurrence of d-aspartic acid in rat brain pineal gland. Biomed Chromatogr 9(2):106–109PubMedCrossRefGoogle Scholar
  41. Imai K, Fukushima T, Santa T, Homma H, Sugihara J, Kodama H, Yoshikawa M (1997) Accumulation of radioactivity in rat brain and peripheral tissues including salivary gland after intravenous administration of 14C-d-aspartic acid. Proc Jpn Acad Ser B 73:48–52CrossRefGoogle Scholar
  42. Ishio S, Yamada H, Hayashi M, Yatsushiro S, Noumi T, Yamaguchi A, Moriyama Y (1998) d-Aspartate modulates melatonin synthesis in rat pinealocytes. Neurosci Lett 249(2–3):143–146PubMedCrossRefGoogle Scholar
  43. Kato S, Ikuta T, Hemmi H, Takahashi S, Kera Y, Yoshimura T (2012) Enzymatic assay for d-aspartic acid using d-aspartate oxidase and oxaloacetate decarboxylase. Biosci Biotechnol Biochem 76(11):2150–2152PubMedCrossRefGoogle Scholar
  44. Kera Y, Aoyama H, Watanabe N, Yamada RH (1996) Distribution of d-aspartate oxidase and free d-glutamate and d-aspartate in chicken and pigeon tissues. Comp Biochem Physiol B Biochem Mol Biol 115(1):121–126PubMedCrossRefGoogle Scholar
  45. Lamanna C, Assisi L, Botte V, Di Fiore MM (2006) Endogenous testicular d-aspartic acid regulates gonadal aromatase activity in boar. J Endocrinol Invest 29(2):141–146PubMedGoogle Scholar
  46. Lamanna C, Assisi L, Botte V, Di Fiore MM (2007a) Involvement of d-Asp in P450 aromatase activity and estrogen receptors in boar testis. Amino Acids 32(1):45–51PubMedCrossRefGoogle Scholar
  47. Lamanna C, Assisi L, Vittoria A, Botte V, Di Fiore MM (2007b) d-Aspartic acid and nitric oxide as regulators of androgen production in boar testis. Theriogenology 67(2):249–254PubMedCrossRefGoogle Scholar
  48. Lee JA, Homma H, Sakai K, Fukushima T, Santa T, Tashiro K, Iwatsubo T, Yoshikawa M, Imai K (1997) Immunohistochemical localization of d-aspartate in the rat pineal gland. Biochem Biophys Res Commun 231(2):505–508PubMedCrossRefGoogle Scholar
  49. Lee JA, Homma H, Tashiro K, Iwatsubo T, Imai K (1999) d-Aspartate localization in the rat pituitary gland and retina. Brain Res 838(1–2):193–199PubMedCrossRefGoogle Scholar
  50. Lee JA, Long Z, Nimura N, Iwatsubo T, Imai K, Homma H (2001) Localization, transport, and uptake of d-aspartate in the rat adrenal and pituitary glands. Arch Biochem Biophys 385(2):242–249PubMedCrossRefGoogle Scholar
  51. Long Z, Homma H, Lee JA, Fukushima T, Santa T, Iwatsubo T, Yamada R, Imai K (1998) Biosynthesis of d-aspartate in mammalian cells. FEBS Lett 434(3):231–235PubMedCrossRefGoogle Scholar
  52. Long Z, Lee JA, Okamoto T, Nimura N, Imai K, Homma H (2000) d-Aspartate in a prolactin-secreting clonal strain of rat pituitary tumor cells (GH(3)). Biochem Biophys Res Commun 276(3):1143–1147PubMedCrossRefGoogle Scholar
  53. Long Z, Sekine M, Adachi M, Furuchi T, Imai K, Nimura N, Homma H (2002) Cell density inversely regulates d- and l-aspartate levels in rat pheochromocytoma MPT1 cells. Arch Biochem Biophys 404(1):92–97PubMedCrossRefGoogle Scholar
  54. Macchia G, Topo E, Mangano N, D’Aniello E, Boni R (2010) dl-Aspartic acid administration improves semen quality in rabbit bucks. Anim Reprod Sci 118(2–4):337–343PubMedCrossRefGoogle Scholar
  55. Masuda W, Nouso C, Kitamura C, Terashita M, Noguchi T (2003) Free d-aspartic acid in rat salivary glands. Arch Biochem Biophys 420(1):46–54PubMedCrossRefGoogle Scholar
  56. Monteforte R, Santillo A, Di Giovanni M, D’Aniello A, Di Maro A, Chieffi Baccari G (2009) d-Aspartate affects secretory activity in rat Harderian gland: molecular mechanism and functional significance. Amino Acids 37:653–664PubMedCrossRefGoogle Scholar
  57. Moriyama Y, Yamada H, Hayashi M, Oda T, Yamaguchi A (1998) Identification of d-aspartate in rat pheochromocytoma PC12 cells. Neurosci Lett 248(1):57–60PubMedCrossRefGoogle Scholar
  58. Nagata Y, Homma H, Lee J-A, Imai K (1999a) d-Aspartate stimulation of testosterone synthesis in rat Leydig cells. FEBS Lett 444:160–164PubMedCrossRefGoogle Scholar
  59. Nagata Y, Homma H, Matsumoto M, Imai K (1999b) Stimulation of steroidogenic acute regulatory (StAR) gene expression by d-aspartate in rat Leydig cells. FEBS Lett 454:317–320PubMedCrossRefGoogle Scholar
  60. Nakatsuka S, Hayashi M, Muroyama A, Otsuka M, Kozaki S, Yamada H, Moriyama Y (2001) d-Aspartate is stored in secretory granules and released through a Ca(2+)-dependent pathway in a subset of rat pheochromocytoma PC12 cells. J Biol Chem 276(28):26589–26596PubMedCrossRefGoogle Scholar
  61. Osamura S (2000) Studies on peroxisomal d-asparate oxidase in rat salivary glands. J Kyushu Dent Soc 54:86–94Google Scholar
  62. Ota N, Shi T, Sweedler JV (2012) d-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems. Amino Acids 43(5):1873–1886PubMedCentralPubMedCrossRefGoogle Scholar
  63. Pampillo M, Theas S, Duvilanski B, Seilicovich A, Lasaga M (2002) Effect of ionotropic and metabotropic glutamate agonists and d-aspartate on prolactin release from anterior pituitary cells. Exp Clin Endocrinol Diabetes 110(3):138–144PubMedCrossRefGoogle Scholar
  64. Raucci F, Di Fiore MM (2009) The reproductive activity in the testis of Podarcis s. sicula involves d-aspartic acid: a study on c-kit receptor protein, tyrosine kinase activity and PCNA protein during annual sexual cycle. Gen Comp Endocrinol 161(3):373–383PubMedCrossRefGoogle Scholar
  65. Raucci F, Di Fiore MM (2010) The maturation of oocyte follicular epithelium of Podarcis s. sicula is promoted by d-aspartic acid. J Histochem Cytochem 58(2):157–171PubMedCentralPubMedCrossRefGoogle Scholar
  66. Raucci F, Di Fiore MM (2011) d-Asp: a new player in reproductive endocrinology of the amphibian Rana esculenta. J Chromatogr B Anal Technol Biomed Life Sci 879(29):3268–3276CrossRefGoogle Scholar
  67. Raucci F, Monteforte R, Di Fiore MM, Chieffi Baccari G (2003) d-Aspartic acid induces merocrine secretion in the frog harderian gland. Rend Fis Acc Lincei 14:205–215CrossRefGoogle Scholar
  68. Raucci F, Assisi L, D’Aniello S, Spinelli P, Botte V, Di Fiore MM (2004) Testicular endocrine activity is upregulated by d-aspartic acid in the green frog, Rana esculenta. J Endocrinol 182:365–376PubMedCrossRefGoogle Scholar
  69. Raucci F, Santillo A, D’Aniello A, Chieffi P, Chieffi Baccari G (2005a) d-Aspartate modulates transcriptional activity in Harderian gland of frog, Rana esculenta: morphological and molecular evidence. J Cell Physiol 204(2):445–454PubMedCrossRefGoogle Scholar
  70. Raucci F, D’Aniello S, Di Fiore MM (2005b) Endocrine roles of d-aspartic acid in the testis of lizard Podarcis s. sicula. J Endocrinol 187(3):347–359PubMedCrossRefGoogle Scholar
  71. Rossi P, Albanesi C, Grimaldi P, Geremia R (1991) Expression of the mRNA for the ligand of c-kit in mouse Sertoli cells. Biochem Biophys Res Com 176:910–914PubMedCrossRefGoogle Scholar
  72. Sakai K, Homma H, Lee JA, Fukushima T, Santa T, Tashiro K, Iwatsubo T, Imai K (1997) d-Aspartic acid localization during postnatal development of rat adrenal gland. Biochem Biophys Res Commun 235(2):433–436PubMedCrossRefGoogle Scholar
  73. Sakai K, Homma H, Lee J-A, Fukushima T, Santa T, Tashiro K, Iwatsubo T, Imai K (1998) Localization of d-aspartic acid in elongate spermatids in rat testis. Arch Biochem Biophys 351:96–105PubMedCrossRefGoogle Scholar
  74. Santillo A, Monteforte R, Raucci F, D’Aniello A, Chieffi Baccari G (2006) Occurrence of d-aspartate in the harderian gland of Podarcis s. sicula and its effect on gland secretion. J Exp Zool A Comp Exp Biol 305(8):610–619PubMedCrossRefGoogle Scholar
  75. Santillo A, Monteforte R, De Lange P, Lanni A, Farina P, Chieffi Baccari G (2008) Dimorphic expression of uncoupling protein-3 in golden hamster harderian gland: effects of castration and testosterone administration. J Cell Physiol 215:481–487PubMedCrossRefGoogle Scholar
  76. Santillo A, Burrone L, Senese R, Cioffi F, Lanni A, Chieffi Baccari G (2011) Effect of d-aspartate uptake on uncoupling protein-3 and α-tubulin expressions in rat Harderian gland. J Chromatogr B Analyt Technol Biomed Life Sci 879:3344–3348PubMedCrossRefGoogle Scholar
  77. Santillo A, Pinelli C, Burrone L, Chieffi Baccari G, Di Fiore MM (2013) d-Aspartic acid implication in the modulation of frog brain sex steroid levels. Gen Comp Endocrinol 181:72–76PubMedCrossRefGoogle Scholar
  78. Santillo A, Falvo S, Chieffi P, Burrone L, Chieffi Baccari G, Longobardi S, Di Fiore MM (2014) d-Aspartate affects NMDA receptor-extracellular signal-regulated kinase pathway and upregulates androgen receptor expression in the rat testis. Theriogenology 81(5):744–751PubMedCrossRefGoogle Scholar
  79. Schell MJ, Cooper OB, Snyder SH (1997) d-Aspartate localizations imply neuronal and neuroendocrine roles. Proc Natl Acad Sci USA 94(5):2013–2018PubMedCentralPubMedCrossRefGoogle Scholar
  80. Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD et al (1994) Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 15:342–355PubMedGoogle Scholar
  81. Takigawa Y, Homma H, Lee J-A, Fukushima T, Santa T, Iwatsubo T, Imai K (1998) d-Aspartate uptake into cultured rat pinealocytes and the concomitant effect on l-aspartate levels and melatonin secretion. Biochem Biophys Res Commun 248:641–647PubMedCrossRefGoogle Scholar
  82. Talevi R, Barbato V, Fiorentino I, Braun S, Longobardi S, Gualtieri R (2013) Protective effects of in vitro treatment with zinc, d-aspartate and coenzyme q10 on human sperm motility, lipid peroxidation and DNA fragmentation. Reprod Biol Endocrinol 11:81–88PubMedCentralPubMedCrossRefGoogle Scholar
  83. Topo E, Soricelli A, D’Aniello A, Ronsini S, D’Aniello G (2009) The role and molecular mechanism of d-aspartic acid in the release and synthesis of LH and testosterone in humans and rats. Reprod Biol Endocrinol 7:120PubMedCentralPubMedCrossRefGoogle Scholar
  84. Topo E, Fisher G, Sorricelli A, Errico F, Usiello A, D’Aniello A (2010) Thyroid hormones and d-aspartic acid, d-aspartate oxidase, d-aspartate racemase, H2O2, and ROS in rats and mice. Chem Biodivers 7(6):1467–1478PubMedCrossRefGoogle Scholar
  85. Wang H, Wolosker H, Pevsner J, Snyder SH, Selkoe DJ (2000) Regulation of rat magnocellular neurosecretory system by d-aspartate: evidence for biological role(s) of a naturally occurring free D-amino acid in mammals. J Endocrinol 167(2):247–252PubMedCrossRefGoogle Scholar
  86. Wang H, Wolosker H, Morris JF, Pevsner J, Snyder SH, Selkoe DJ (2002) Naturally occurring free d-aspartate is a nuclear component of cells in the mammalian hypothalamo-neurohypophyseal system. Neuroscience 109(1):1–4PubMedCrossRefGoogle Scholar
  87. Weaver CD, Gundersen V, Verdoorn TA (1998) A high affinity glutamate/aspartate transport system in pancreatic islets of Langerhans modulates glucose-stimulated insulin secretion. J Biol Chem 273(3):1647–1653PubMedCrossRefGoogle Scholar
  88. Weil ZM, Huang AS, Beigneux A, Kim PM, Molliver ME, Blackshaw S, Young SG, Nelson RJ, Snyder SH (2006) Behavioural alterations in male mice lacking the gene for d-aspartate oxidase. Behav Brain Res 171(2):295–302PubMedCrossRefGoogle Scholar
  89. Wolosker H, D’Aniello A, Snyder SH (2000) d-Aspartate disposition in neuronal and endocrine tissues: ontogeny, biosynthesis and release. Neuroscience 100(1):183–189PubMedCrossRefGoogle Scholar
  90. Yamada H, Yatsushiro S, Yamamoto A, Hayashi M, Nishi T, Futai M, Yamaguchi A, Moriyama Y (1997) Functional expression of a GLT-1 type Na+-dependent glutamate transporter in rat pinealocytes. J Neurochem 69(4):1491–1498PubMedCrossRefGoogle Scholar
  91. Yamamoto A, Tanaka H, Ishida T, Horiike K (2010) d-Aspartate oxidase localisation in pituitary and pineal glands of the female pig. J Neuroendocrinol 22(11):1165–1172PubMedCrossRefGoogle Scholar
  92. Yatsushiro S, Yamada H, Kozaki S, Kumon H, Michibata H, Yamamoto A, Moriyama Y (1997) l-Aspartate but not the D form is secreted through microvesicle-mediated exocytosis and is sequestered through Na+-dependent transporter in rat pinealocytes. J Neurochem 69(1):340–347PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Maria Maddalena Di Fiore
    • 1
    Email author
  • Alessandra Santillo
    • 1
  • Gabriella Chieffi Baccari
    • 1
  1. 1.Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e FarmaceuticheSeconda Università di NapoliCasertaItaly

Personalised recommendations