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Type: Artigo de periódico
Title: Inhibition of heparin synthesis by methotrexate in rats in vivo
Author: Marcondes, S
Bau, EC
Antunes, E
Dietrich, CP
Nader, HB
De Nucci, G
Abstract: The content and synthesis of heparin and mast cell-dependent skin oedema (as an indirect evaluation of histamine and serotonin content) were investigated in the rat skin after chronic treatment with compound 48/80, a mast cell degranulating substance. The effect of methotrexate, a folic acid analogue that interrupts the synthesis of DNA and RNA, on heparin synthesis and amine storage also was evaluated in rat skin. The heparin content at 6 and 240 hr after treatment with compound 48/80 was reduced markedly (86 and 64%, respectively). At 6 hr, heparin synthesis increased 3.1-fold compared with control animals; maximal synthesis occurred at 24 hr post-treatment (12.8-fold increase), decaying at 240 hr (2.4-fold increase). The dermatan sulfate content and synthesis were not affected by treatment with compound 48/80. Autoradiographic analysis revealed that methotrexate (2.5 mg/kg for 3 consecutive days) abolished heparin synthesis at 6, 24, and 72 hr after compound 48/80 treatment, without affecting dermatan sulfate synthesis. The oedema induced by intradermal injection of compound 48/80 (1 mug/site) into the rat skin was decreased significantly at 6 hr after chronic treatment with this compound, but was restored completely 72 hr post-treatment. This pattern of oedematogenic response was also observed in the methotrexate-treated rats. In conclusion, our results show that methotrexate suppresses heparin synthesis without affecting the synthesis of either dermatan sulfate or the co-stored amines histamine/serotonin (as evaluated by measuring the mast cell-dependent oedema), suggesting that the enzyme system involved in heparin synthesis is inducible. (C) 2002 Elsevier Science Inc. All rights reserved.
Subject: mast cells
heparin synthesis
compound 48/80
Country: Inglaterra
Editor: Pergamon-elsevier Science Ltd
Rights: fechado
Identifier DOI: 10.1016/S0006-2952(02)01063-8
Date Issue: 2002
Appears in Collections:Unicamp - Artigos e Outros Documentos

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