Synthesis and evaluation of lysophosphatidylserine analogues as inducers of mast cell degranulation. Potent activities of lysophosphatidylthreonine and its 2-deoxy derivative

Masazumi Iwashita, Kumiko Makide, Taro Nonomura, Yoshimasa Misumi, Yuko Otani, Mayuko Ishida, Ryo Taguchi, Masafumi Tsujimoto, Junken Aoki, Hiroyuki Arai, Tomohiko Ohwada

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

In response to various exogenous stimuli, mast cells (MCs) release a wide variety of inflammatory mediators stored in their cytoplasmic granules and this release initiates subsequent allergic reactions. Lysophosphatidylserine (lysoPS) has been known as an exogenous inducer to potentiate histamine release from MCs, though even at submicromolar concentrations. In this study, through SAR studies on lysoPS against MC degranulation, we identified lysoPT, a threonine-containing lysophospholipid and its 2-deoxy derivative as novel strong agonists. LysoPT and its 2-deoxy derivative induced histamine release from MCs both in vitro and in vivo at a concentration less than one-tenth that of lysoPS. Notably, lysoPT did not activate a recently proposed lysoPS receptor on MCs, GPR34, demonstrating the presence of another undefined receptor reactive to both lysoPS and lysoPT that is involved in MC degranulation. Thus, the present strong agonists, lysoPT and its 2-deoxy derivative, will be useful tools to understand the mechanisms of lysoPS-induced activation of degranulation of MCs.

Original languageEnglish
Pages (from-to)5837-5863
Number of pages27
JournalJournal of Medicinal Chemistry
Volume52
Issue number19
DOIs
Publication statusPublished - 2009 Oct 8

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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