Developments in Tryptophan and Serotonin Metabolism by Osamu Hayaishi’ (auth.), Graziella Allegri, Carlo V. L.

By Osamu Hayaishi’ (auth.), Graziella Allegri, Carlo V. L. Costa, Eugenio Ragazzi, Hans Steinhart, Luigi Varesio (eds.)

This quantity includes the court cases of the 10th foreign assembly of the foreign research staff for Tryptophan examine (ISTR V), held on the college of Padova, Padova, Italy, from 25-29 June, 2002 below the auspices of the Ministry of schooling, collage and examine (MIUR) in Roma, the collage of Padova, the Italian Chemical Society - department of Pharmaceutical Chemistry, the Veneto zone and town of Padova. The assembly was once geared up to hide the new advancements within the box of tryptophan examine. Weare very honoured that such a lot of audio system approved our invitation to provide plenary lectures which, with the opposite communications, proven the excessive clinical worth of the assembly. The guides during this quantity are subdivided into 9 major chapters, and canopy the entire significant features in immunology, neurobiology, psychiatry, pathology, clinics, metabolism, enzymology, pharmacology, toxicology, melatonin, workout and analytical chemistry. the quantity contains the contributions of 325 scientists from 24 international locations, and the Musajo Memorial Lecture introduced by way of Prof. Osamu Hayaishi in the course of the commencing Ceremony.

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S the astrocyte line NHA4631 produced nitric oxide upon co-stimulation. In contrast in the line H21/92 no production of NO was detectable by measuring nitrite in culture supernatants. To analyze iNOS induction in more detail we used the more sensitive RT peR reaction. S the cell line NHA4631 22 C. OBERDORFER ET AL. express iNOS mRNA and in addition the cell line H21192 which no detectable NO was found did express iNOS mRNA after appropriate stimulation. Regulatory role of nitric oxide on IFN-y induced IDO activity: It has been described that IDO activity is inhibited in the presence of nitric oxide in murine macrophages 20 and on the other hand that iNOS is involved in the antiparasitic defense of human astrocytes 7• We therefore were interested in analyzing the over all effect of a combined IDO/iNOS activation.

Quinolinic acid is active as a stimulator of NMDAreceptors while kynurenic acid dampens the receptor activity. Therefore IDO, like iNOS, is involved in the regulation of neuronal activity, and it is assumed that IDO also mediates neurodegenerative and neurotoxic effects 14. It has been described that human astrocytes express iNOS activity after appropriate stimulation l5 , and that the production of nitric oxide is involved in the defense against toxoplasma and cryptococcus. Human astrocytoma cells are also endowed with an IFN-y inducible IDO activityl6, however antimicrobial effects mediated by IDO positive astrocytes have not yet been analyzed.

The failure of tryptophan to antagonize toxoplasmostasis in murine astrocytes derived from iNOS deficient rrllce is a strong argument against an involvement of IDO in the defense of murine astrocytes against Toxoplasma gondii. Furthennore, Halonen et ae 6 showed that the activation of murine astrocytes results in the activation of a toxoplasmocidal effect, in contrast the toxoplasmostatic IDO mediated antiparasitic effect in human astrocytoma cells. Therefore it could be assumed that the effector-mechanism activated in murine astrocytes is neither iNOS nor IDO but a third unknown mechanism.

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