Involvement of endothelin and ETA endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation
Involvement of endothelin and ETA endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation
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DOI：
10.1254/jphs.fp0072051
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发表时间：
2008-02-01
影响因子：
3.5
通讯作者：
Kuraishi, Yasushi
中科院分区：
文献类型：
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作者：
Fujita, Masahide;Andoh, Tsugunobu;Kuraishi, Yasushi
我们研究了内皮素（ET）是否会参与小鼠皮肤癌疼痛。原位接种B16-BL 6黑色素瘤细胞到C57 BL/6小鼠后爪的足底区域中产生显著的机械性异常性疼痛。跖内注射ETA受体拮抗剂BQ-123（0.3 - 3 nmol/部位），但不注射ETB受体拮抗剂BQ-788（1和3 nmol/部位），可抑制生长黑色素瘤小鼠的机械性异常性疼痛。在幼稚小鼠中，足底注射从爪中生长的黑素瘤制备的肿瘤提取物（1和3 mg/部位）产生机械性异常性疼痛，其被剂量为3和10 nmol/部位的BQ-123和BQ-788抑制。足底注射ET-1（1和10 pmol/网站）引起舔行为，这是在黑色素瘤轴承后爪增加。BQ-123（3和10 nmol/部位）抑制ET-1（10 pmol/部位）诱导的舔体。接种侧背根神经节ETA受体mRNA水平显著升高，而ETB受体mRNA水平无显著变化。培养的B16-BL 6细胞中含有ET，随着黑色素瘤体积的增大，ET的含量也随之增加。这些结果表明ET-1和ETA受体至少部分参与了黑色素瘤细胞接种引起的疼痛的诱导。
We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ETA-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but not the ETB-receptor antagonist BQ-788 (I and 3 nmol/site), inhibited mechanical allodynia in mice with grown melanoma. In naive mice, an intraplantar injection of tumor extract(1 and 3 mg/site), which was prepared from the grown melanoma in the paw, produced mechanical allodynia, which was inhibited by BQ-123 and BQ-788 at doses of 3 and 10 nmol/site. An intraplantar injection of ET-1 (1 and 10 pmol/site) elicited licking behavior, which was increased in the melanoma-bearing hind paw. BQ-123 (3 and 10 nmol/site) inhibited licking induced by ET-1(10 pmol/site). The level of mRNA of ETA, but not ETB, receptor, was significantly increased in the dorsal root ganglia on the inoculated side. Cultured B16-BL6 cells contained ET, and the melanoma mass increased the concentration of ET as it grew bigger. These results suggest that ET-1 and ETA receptor are at least partly involved in the induction of pain induced by melanoma cell inoculation.