In a concerted action kit ligand and interleukin 3 control the synthesis of serotonin in murine bone marrow-derived mast cells. Up-regulation of GTP cyclohydrolase I and tryptophan 5-monooxygenase activity by the kit ligand
| Autor: | I, Ziegler, L, Hültner, D, Egger, B, Kempkes, R, Mailhammer, S, Gillis, W, Rödl |
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| Rok vydání: | 1993 |
| Předmět: |
Mice
Inbred BALB C Serotonin Stem Cell Factor Bone Marrow Cells Tryptophan Hydroxylase Hematopoietic Cell Growth Factors Biopterin Models Biological Recombinant Proteins 5-Hydroxytryptophan Kinetics Mice Bone Marrow Animals Interleukin-3 Interleukin-4 Mast Cells GTP Cyclohydrolase Cells Cultured Chromatography High Pressure Liquid |
| Zdroj: | The Journal of biological chemistry. 268(17) |
| ISSN: | 0021-9258 |
| Popis: | Mouse bone marrow-derived mast cells (BMMC) store and release serotonin whose synthesis is initiated by tryptophan 5-monooxygenase. (6R)-H4biopterin serves as the natural cofactor for this reaction. GTP cyclohydrolase I catalyzes the first and rate-limiting step of its synthesis. In this study we demonstrate that among a panel of growth-promoting cytokines including kit ligand (KL), interleukin 3 (IL-3), IL-4, IL-9, and nerve growth factor, KL selectively enhances the synthesis of H4biopterin through up-regulation of GTP cyclohydrolase I activity to 6.2-fold levels. The activities of the subsequent enzymes 6-pyruvoyl-H4pterin synthase and sepiapterin reductase remain unaffected. The activity of tryptophan 5-monooxygenase was selectively enhanced 4.5-fold by the combination of IL-3 with KL. All other factors could not substitute for KL. The constitutive high activity of aromatic L-amino acid decarboxylase is not different in cells cultured in IL-3 and/or KL. In consequence, the concerted action of IL-3 and KL on the GTP cyclohydrolase I and the tryptophan 5-monooxygenase reaction enhances the production of serotonin to about 20-fold levels. Additionally, KL specifically causes the release of about half of total serotonin produced. Hence, our data demonstrate a novel role of these cytokines for the function of mouse BMMC and provide a coherent view of the regulation of serotonin synthesis in this cell type. |
| Databáze: | OpenAIRE |
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