Inhibition of heparin synthesis by methotrexate in rats in vivo

Inhibition of heparin synthesis by methotrexate in rats in vivo

Author Marcondes, S. Google Scholar
Bau, E. C. Google Scholar
Antunes, E. Google Scholar
Dietrich, C. P. Google Scholar
Nader, H. B. Google Scholar
De Nucci, G. Google Scholar
Institution Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de São Paulo (UNIFESP)
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.
Keywords mast cells
heparin synthesis
compound 48/80
Language English
Date 2002-07-15
Published in Biochemical Pharmacology. Oxford: Pergamon-Elsevier B.V., v. 64, n. 2, p. 169-175, 2002.
ISSN 0006-2952 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 169-175
Access rights Closed access
Type Article
Web of Science ID WOS:000177233400002

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