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

Abstract

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-Aspartate Prevents Corticostriatal Long-Term Depression and Attenuates Schizophrenia-Like Symptoms Induced by Amphetamine and MK-801

“…The determination of D-aspartate was performed by HPLC, based on the diastereomeric separation of D-aspartate from the L-form and other L-amino acids, as described previously (D'Aniello et al, 2000). Data were analyzed with a Student's t test and expressed as means Ϯ SEM.…”

Endocrine roles of d-aspartic acid in the testis of lizard Podarcis s. sicula

“…-Asp is the precursor for the synthesis of N-methyl-D-aspartic acid (NMDA) and the enzyme catalyzing this reaction is the N-methyl transferase, as reported in previous work carried out in rats (D'Aniello et al 2000a,b). -Asp is localized in various neurons of rat brain, including the hippocampus, and in the hypothalamo-neurohypophyseal system suggesting its involvement in regulating the neurosecretory system (Schell et al 1997, D'Aniello et al 2000a, Wang et al 2000. In vertebrates, this amino acid occurs in the nervous tissues of chickens (Neidle & Dunlop 1990), rats (Dunlop et al 1986, D'Aniello et al 1993, 2000a,b, Hashimoto et al 1993 and humans (Fisher et al 1991(Fisher et al , 1994).…”

Gas chromatographic quantification of free D‐amino acids in higher vertebrates

“…For the relevance of d-amino acids to nutritional and physiological aspects see the comprehensive review by Friedman (1999), for the analytical chemistry and biochemistry see the overview by Imai et al (1996), and for plant d-amino acids to a report by Brückner and Westhauser (2003). New areas of interest of d-amino acids are, for example, the genesis of d-amino acids and mode of action of the resulting antimicrobial peptides found in skin secretions of frogs belonging to the genus Bombina, or neuropeptides of molluscs belonging to species of genera such as Achatina, Helix or Conus (Jolles, 1998), the role of free and N-methylated d-amino acids in nervous and brain tissues (D'Aniello et al, 2000) or aspartate isomerization in human lens proteins (Fujii et al, 1999).…”