Activation of protein kinase C reverses capsaicin-induced calcium-dependent desensitization of TRPV1 ion channels
Activation of protein kinase C reverses capsaicin-induced calcium-dependent desensitization of TRPV1 ion channels
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DOI：
10.1016/j.ceca.2003.11.003
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发表时间：
2004-05-01
期刊：
影响因子：
4
通讯作者：
Roufogalis, BD
中科院分区：
文献类型：
--
作者：
Mandadi, S;Numazaki, M;Roufogalis, BD
辣椒素敏感的背根神经节（DRG）神经元和TRPV 1转染的中国仓鼠卵巢（CHO）细胞中香草素受体亚型1（TRPV 1）的钙选择性离子通道在连续应用100 nM辣椒素诱导的钙依赖性快速耐受后脱敏。在细胞外钙缺乏的情况下，没有观察到TRPV 1对100 nM辣椒素刺激的快速耐受。应用佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）恢复脱敏TRPV 1离子通道的辣椒素敏感性。PMA诱导的脱敏TRPV 1的恢复主要是由于在脱敏后重新应用辣椒素期间观察到的细胞外钙的流入。辣椒平阻断PMA对辣椒素的再致敏作用。蛋白激酶C（PKC）抑制肽PKC片段19-36也抑制PMA对辣椒素的再致敏作用。PMA对辣椒素诱导的脱敏的抑制作用可通过TRPV 1的突变来阻止，其中磷酸化位点丝氨酸502和丝氨酸800被丙氨酸取代。本研究为PKC在逆转辣椒素诱导的TRPV 1离子通道钙依赖性脱敏中的作用提供了证据。(C)2003 Elsevier Ltd.保留所有权利。
Ca2+ selective ion channels of vanilloid receptor subtype-1 (TRPV1) in capsaicin-sensitive dorsal root ganglion (DRG) neurons and TRPV1 transfected Chinese hamster ovarian (CHO) cells are desensitized following calcium-dependent tachyphylaxis induced by successive applications of 100nM capsaicin. Tachyphylaxis of TRPV1 to 100nM capsaicin stimuli was not observed in the absence of extracellular calcium. Capsaicin sensitivity of desensitized TRPV1 ion channels recovered on application of phorbol-12-myristate-13-acetate (PMA). PMA-induced recovery of desensitized TRPV1 was primarily due to influx of extracellular calcium observed during re-application of capsaicin following desensitization. Capsazepine blocked the re-sensitization to capsaicin by PMA. Protein kinase C (PKC) inhibitory peptide PKC fragment 19-36 also inhibited re-sensitization to capsaicin by PMA. Reversal of capsaicin-induced desensitization by PMA was prevented by a mutation of TRPV1 where phosphorylation sites serine502 and serine800 were replaced with alanine. This study provides evidence for a role of PKC in reversing capsaicin-induced calcium-dependent desensitization of TRPV1 ion channels. (C) 2003 Elsevier Ltd. All rights reserved.