PMID- 10744627 OWN - NLM STAT- MEDLINE DCOM- 20000501 LR - 20190516 IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 14 IP - 5 DP - 2000 Apr TI - 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. PG - 699-714 AB - 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 approximately 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. FAU - D'Aniello, A AU - D'Aniello A AD - Department of Biochemistry and Molecular Biology and Neurobiology, Zoological Station 'A. Dohrn', 80121, Napoli, Italy. daniello@alpha.snz.it FAU - Di Fiore, M M AU - Di Fiore MM FAU - Fisher, G H AU - Fisher GH FAU - Milone, A AU - Milone A FAU - Seleni, A AU - Seleni A FAU - D'Aniello, S AU - D'Aniello S FAU - Perna, A F AU - Perna AF FAU - Ingrosso, D AU - Ingrosso D LA - eng GR - GM TW00033/GM/NIGMS NIH HHS/United States GR - SO6GM45455/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 30KYC7MIAI (Aspartic Acid) RN - 33515-09-2 (Gonadotropin-Releasing Hormone) RN - 6384-92-5 (N-Methylaspartate) RN - 9002-67-9 (Luteinizing Hormone) RN - 9002-72-6 (Growth Hormone) SB - IM MH - Animals MH - Aspartic Acid/*metabolism/pharmacology MH - Circadian Rhythm MH - Gonadotropin-Releasing Hormone/metabolism MH - Growth Hormone/*metabolism MH - Hypothalamus/drug effects/physiology MH - In Vitro Techniques MH - Luteinizing Hormone/*metabolism MH - Male MH - N-Methylaspartate/*metabolism/pharmacology MH - Neurosecretory Systems/drug effects/*physiology MH - Pituitary Gland, Anterior/drug effects/physiology MH - Rats MH - Rats, Wistar MH - Tissue Distribution EDAT- 2000/04/01 09:00 MHDA- 2000/05/08 09:00 CRDT- 2000/04/01 09:00 PHST- 2000/04/01 09:00 [pubmed] PHST- 2000/05/08 09:00 [medline] PHST- 2000/04/01 09:00 [entrez] AID - 10.1096/fasebj.14.5.699 [doi] PST - ppublish SO - FASEB J. 2000 Apr;14(5):699-714. doi: 10.1096/fasebj.14.5.699.