HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by D’ANIELLO, A. Articles by INGROSSO, D. Search for Related Content PubMed PubMed Citation Articles by D’ANIELLO, A. Articles by INGROSSO, D.

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

ANTIMO D’ANIELLO^*1, M. MADDALENA DI FIORE^*,, GEORGE H. FISHER, ALFREDO MILONE^§, ANGELO SELENI^|, SALVATORE D’ANIELLO^*, ALESSANDRA F. PERNA^** and DIEGO INGROSSO

^* Department of Biochemistry and Molecular Biology and Neurobiology, Zoological Station ‘A. Dohrn’, 80121, Napoli, Italy;
Department of Scienze della Vita, Second University of Naples, 81100, Caserta, Italy;
Department of Chemistry, Barry University, Miami Shores, Florida 33161, USA;
^§ Institute of Chemistry of Molecule of Biological Interest, CNR, 80072, Arco Felice, Napoli, Italy;
^| Department of Radioimmunology, Laboratorio Igea, 80027, Frattamaggiore, Napoli, Italy;
^** Institute of Nephrology, School of Medicine, II University of Naples, 80131 Napoli, Italy; and
Institute of Biochemistry of Macromolecules, School of Medicine, II University of Naples, 80138 Napoli, Italy

¹Correspondence: Stazione Zoologica ‘A. Dohrn’, Villa Comunale 1, 80121 Napoli, Italy. E-mail: daniello{at}alpha.snz.it

Using two specific and sensitive fluorometric/HPLC methods and a GC-MS method, alone and in combination with D-aspartate oxidase, we have demonstrated for the first time that N-methyl-D-aspartate (NMDA), in addition to D-aspartate (D-Asp), is endogenously present as a natural molecule in rat nervous system and endocrine glands. Both of these amino acids are mostly concentrated at nmol/g levels in the adenohypophysis, hypothalamus, brain, and testis. The adenohypophysis maximally showed the ability to accumulate D-Asp when the latter is exogenously administered. In vivo experiments, consisting of the i.p. injection of D-Asp, showed that D-Asp induced both growth hormone and luteinizing hormone (LH) release. However, in vitro experiments showed that D-Asp was able to induce LH release from adenohypophysis only when this gland was co-incubated with the hypothalamus. This is because D-Asp also induces the release of GnRH from the hypothalamus, which in turn is directly responsible for the D-Asp-induced LH secretion from the pituitary gland. Compared to D-Asp, NMDA elicits its hormone release action at concentrations ~100-fold lower than D-Asp. D-AP5, a specific NMDA receptor antagonist, inhibited D-Asp and NMDA hormonal activity, demonstrating that these actions are mediated by NMDA receptors. NMDA is biosynthesized from D-Asp by an S-adenosylmethionine-dependent enzyme, which we tentatively denominated as NMDA synthase.—D’Aniello, A., Di Fiore, M. M., Fisher, G. H., Milone, A., Seleni, A., D’Aniello, S., Perna, A. F., Ingrosso, D. 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.

Key Words: D-Asp • NMDA • methyltransferase • S-adenosylmethionine • NMDA synthase • testosterone • progesterone • endocrine glands • nervous system

This article has been cited by other articles:

				G. D'Aniello, N. Grieco, M.A. Di Filippo, F. Cappiello, E. Topo, E. D'Aniello, and S. Ronsini Reproductive implication of D-aspartic acid in human pre-ovulatory follicular fluid Hum. Reprod., December 1, 2007; 22(12): 3178 - 3183. [Abstract] [Full Text] [PDF]

				A. Yamamoto, H. Tanaka, T. Ishida, and K. Horiike Functional and Structural Characterization of D-Aspartate Oxidase from Porcine Kidney: Non-Michaelis Kinetics due to Substrate Activation J. Biochem., March 1, 2007; 141(3): 363 - 376. [Abstract] [Full Text] [PDF]

				F Raucci, S D'Aniello, and M M Di Fiore Endocrine roles of D-aspartic acid in the testis of lizard Podarcis s. sicula J. Endocrinol., December 1, 2005; 187(3): 347 - 359. [Abstract] [Full Text] [PDF]

				H. Hasegawa, T. Matsukawa, Y. Shinohara, R. Konno, and T. Hashimoto Role of renal D-amino-acid oxidase in pharmacokinetics of D-leucine Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E160 - E165. [Abstract] [Full Text] [PDF]

				S. Nakatsuka, M. Hayashi, A. Muroyama, M. Otsuka, S. Kozaki, H. Yamada, and Y. Moriyama D-Aspartate Is Stored in Secretory Granules and Released through a Ca2+-dependent Pathway in a Subset of Rat Pheochromocytoma PC12 Cells J. Biol. Chem., July 6, 2001; 276(28): 26589 - 26596. [Abstract] [Full Text] [PDF]