Inhibitory effects of GMCHA-OPhBut on phospholipid methylation and histamine release in mast cells activated by concanavalin A, anti-IgE, and antigen.

Abstract:

:[3H]Methyl group incorporation and histamine secretion in rat mast cells induced by anti-IgE and con A were strongly inhibited by trans-4-guanidinomethylcyclohexanecarboxylic acid 4-tert-butylphenyl ester (GMCHA-OPhBut), a strong and specific inhibitor for pH 7 tryptase (Muramatsu et al. (1988) Biol. Chem. Hoppe-Seyler 369, 617-625) which is present in rat mast cells. The IC50s for these events were of the order of 10(-6) M. Addition of GMCHA-OPhBut after the maximal increase in [3H]methyl group incorporation in rat mast cells activated by con A and anti-IgE induced rapid reduction of the methylated phospholipid, and the later histamine release was strongly suppressed. Mast cells were prepared with Mg2+-free Tyrode-HEPES solution, and challenged with anti-IgE with or without Mg2+. With Mg2+, [3H]methyl group incorporation was enhanced, and histamine was secreted time-dependently. Without Mg2+, [3H]methyl group incorporation fell to one-third, whereas histamine secretion was not affected. These results were incompatible with the above results. From these results it was strongly suggested that a trypsin-like protease, probably pH 7 tryptase, is involved not only in the early events, such as activation of phosphatidylethanolamine methyltransferase I and/or II, but also in the late events such as histamine release, and phospholipid methylation is not associated with histamine secretion.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Takei M,Matumoto T,Endo K,Muramatu M

doi

10.1093/oxfordjournals.jbchem.a122642

subject

Has Abstract

pub_date

1989-02-01 00:00:00

pages

219-25

issue

2

eissn

0021-924X

issn

1756-2651

journal_volume

105

pub_type

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