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.
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.
D'Aniello
A
A
Department of Biochemistry and Molecular Biology and Neurobiology, Zoological Station 'A. Dohrn', 80121, Napoli, Italy. daniello@alpha.snz.it
Di Fiore
M M
MM
Fisher
G H
GH
Milone
A
A
Seleni
A
A
D'Aniello
S
S
Perna
A F
AF
Ingrosso
D
D
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism* / Q000494:pharmacology; D002940:Circadian Rhythm; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism* / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000187:drug effects / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D001224:Aspartic Acid; D007987:Gonadotropin-Releasing Hormone; D016202:N-Methylaspartate; D007986:Luteinizing Hormone; D013006:Growth Hormone