Effects of granisetron and vagotomy on c-fos mRNA expression in the rat medulla oblongata as assessed by in situ hybridization

Effects of granisetron and vagotomy on c-fos mRNA expression in the rat medulla oblongata as assessed by in situ hybridization
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DOI:
10.2220/biomedres.25.229
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发表时间:
2004-10-01
影响因子:
1.2
通讯作者:
Iwanaga, T
Iwanaga, T
中科院分区:
医学4区
文献类型:
--
作者:
Endo, T;Minami, M;Iwanaga, T

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癌症化疗引起的恶心和呕吐已被证明涉及体液以及神经机制。5-羟色胺(5-羟色胺,5-HT)在这些机制中的主导作用得到5-HT受体拮抗剂抑制呕吐的支持。应用原位杂交技术比较了5-HT_3受体拮抗剂格拉司琼和迷走神经切断对大鼠尾侧脑干孤束核(NTS)和最后区(AP)c-fos mRNA表达的影响。c-fos mRNA在NTS和AP中的表达在顺铂给药后2 h显著升高。格拉司琼预处理可显著抑制顺铂诱导孤束核c-fos表达。相反,顺铂组和格拉司琼治疗的顺铂组之间AP中的c-fos表达没有差异。迷走神经切断组和假手术组AP和NTS c-fos mRNA表达的诱导程度相似。我们的研究结果表明,c-fos mRNA在NTS的表达可能是由5-HT,受体的特异性控制和非特异性的不道德的因素,如转录活性的调节,在迷走神经切断后,在AP的c-fos表达中起重要作用。
Cancer chemotherapy-induced nausea and vomiting have been demonstrated to involve humoral as well as neuronal mechanisms. A leading role of serotonin (5-hydroxytryptamine, 5-HT) in these mechanisms is supported by inhibition of the emesis by 5-HT, receptor antagonists. We compared the effects of granisetron, a selective 5-HT3 receptor antagonist, and vagotomy on c-fos mRNA expression in the nucleus of the solitary tract (NTS) and the area postrema (AP) of the rat caudal brainstem by means of in situ hybridization. The expression of c-fos mRNA in the NTS and AP was significantly elevated 2 h after cisplatin administration. The induction of c-fos expression by cisplatin in the NTS was significantly inhibited by pretreatment with granisetron. In contrast, the c-fos expression in the AP did not differ between the cisplatin group and the granisetron-treated cisplatin group. The degree of the induction of c-fos mRNA expression in both the AP and NTS was similar between the vagotomy and sham operation groups. Our results suggest that the expression of c-fos mRNA in the NTS may be specifically controlled by 5-HT, receptors and that nonspecific Immoral factors, such as modulation of transcriptional activity, play an important role in c-fos expression in the AP after vagotomy.