Pemirolast potently attenuates paclitaxel hypersensitivity reactions through inhibition of the release of sensory neuropeptides in rats

Yoshinori Itoh, Toshiaki Sendo, Toshio Hirakawa, Shinya Takasaki, Takeshi Goromaru, Hitoo Nakano, Ryozo Oishi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The effects of anti-allergic agents on the hypersensitivity reactions to paclitaxel, an anti-cancer agent, were examined in rats. Intravenous injection of paclitaxel (15 mg/kg) caused a marked extravasation of plasma protein in lungs and a transient decrease in arterial partial oxygen pressure (PaO 2). The paclitaxel-induced protein extravasation was inhibited by low doses (0.1-1 mg/kg) of pemirolast or high doses (30-100 mg/kg) of cromoglycate. However, ketotifen was not effective. The decrease in PaO 2 induced by paclitaxel was also significantly reversed by pemirolast. On the other hand, the paclitaxel-induced plasma extravasation was not attenuated by a histamine H1 blocker diphenhydramine or an H 2 blocker famotidine, but was significantly reduced by a neurokinin NK1 antagonist LY303870 (0.5 mg/kg) and an NK2 antagonist SR48968 (1 mg/kg). The concentrations of proteins and sensory peptides such as substance P, neurokinin A and calcitonin gene-related peptide but not histamine in the rat bronchoalveolar lavage fluid were elevated by paclitaxel injection. Both cromoglycate and pemirolast reduced the paclitaxel-induced rise in proteins and sensory peptides. Therefore, we demonstrated for the first time that sensory nerve peptides are involved in paclitaxel hypersensitivity and that an anti-allergic agent pemirolast attenuates the paclitaxel response by inhibiting the release of sensory nerve peptides.

Original languageEnglish
Pages (from-to)888-894
Number of pages7
JournalNeuropharmacology
Volume46
Issue number6
DOIs
Publication statusPublished - May 1 2004
Externally publishedYes

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Keywords

  • Hypersensitivity
  • Paclitaxel
  • Pemirolast
  • Pulmonary dysfunction
  • Sensory nerve peptides

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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