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ID 27758
本文ファイル
著者
Miyano, Kanako
Tang, He-Bin
Nakamura, Yoki
Inoue, Atsuko
キーワード
DRG cells
Paclitaxel
PKC
sP
Vinorelbine
NDC
医学
抄録(英)
Many patients suffer from serious adverse effects including respiratory distress and pulmonary edema during and after chemotherapy with paclitaxel or vinorelbine. These effects appear to be due to the activation of neurokinin-1 receptors. The present study investigated the influences of paclitaxel and vinorelbine on the substance P (sP) release from cultured dorsal root ganglion (DRG) cells using a radioimmunoassay. Both paclitaxel and vinorelbine evoked sP release in a dose- and time-dependent manner within 60 min at a concentration range of 0.1-10 mu M. The sP release levels induced by the two drugs were attenuated by pretreatment with the protein kinase Cs (PKCs) inhibitors (bisindolyimaieimide I and Go6976). Moreover, the paclitaxel- or vinorelbine-induced sP release was diminished in the absence of extracellular Ca2+ or the presence of LaCl3 (an extracellular Ca2+ influx blocker). A Ca2+ imaging assay further indicated that both paclitaxel and vinorelbine gradually increased the intracellular Ca2+ concentration, and these increases lasted for at least 15 min and were suppressed by Go6976. Paclitaxel caused the membrane translocation of only PKC beta within 10 min after stimulation, whereas vinorelbine induced the translocation of both PKC alpha and beta. The paclitaxel- and vinorelbine-induced sP release levels were separately inhibited by ruthenium red (a transient receptor potential (TRP) channel blocker) and gabapentin (an inhibitor of voltage-gated Ca2+ channels (VGCCs)). These findings suggest that paclitaxel and vinorelbine evoke the sP release from cultured DRG cells by the extracellular Ca2+ influx through TRP channels activated by PKC beta and VGCCs activated by both PKC alpha and beta, respectively.
掲載誌名
Neuropharmacology
57巻
1号
開始ページ
25
終了ページ
32
出版年月日
2009
出版者
Pergamon-Elsevier Science Ltd
ISSN
0028-3908
NCID
出版者DOI
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
author
権利情報
Copyright (c) 2009 Elsevier Ltd
関連情報URL
部局名
医歯薬学総合研究科