Differential effects on gastrointestinal and hepatic vagal afferent fibers in the rat by the anti-cancer agent cisplatin
Differential effects on gastrointestinal and hepatic vagal afferent fibers in the rat by the anti-cancer agent cisplatin
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DOI：
10.1016/j.autneu.2004.08.011
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发表时间：
2004-09-30
影响因子：
2.7
通讯作者：
Friedman, MI
中科院分区：
文献类型：
--
作者：
Horn, CC;Richardson, EJ;Friedman, MI
顺铂，一种癌症化疗药物，像许多毒素一样，会产生呕吐和恶心。腹部迷走神经切断术或57HT(3)受体拮抗剂治疗可阻断顺铂诱导的呕吐，这表明它可以（间接地）激活迷走神经传入纤维上的5-HT3受体。顺铂诱导肠道5-羟色胺（5-HT）大量释放进入肝门静脉，这可能激活门静脉或肝脏的迷走神经传入纤维，引起呕吐或其他治疗副作用（如减少食物摄入量）。本研究通过记录大鼠迷走神经肝总支（CHB）的神经生理反应，探讨顺铂对胃肠道和门静脉/肝迷走神经传入纤维的影响。CHB含有支配胃肠道、门静脉和肝脏的迷走神经传入纤维。顺铂（10mg /kg，颈静脉，j.v.）可增加多单位CHB活性，这种作用可被5- ht3受体拮抗剂（Y-25130, 0.8 mg, j.v.）阻断。切断胃十二指肠分支（GDB），这是CHB的一个亚分支，含有GI传入纤维，导致顺铂治疗产生的多单位CHB放电完全抑制。顺铂敏感的单个单位的活性通过5-HT3受体拮抗剂治疗或切割GDB而降低。相反，顺铂不敏感单位不受5- ht3拮抗剂或GDB消融的影响。本研究结果表明，顺铂通过5-HT3受体激活GI迷走神经传入纤维，但不影响门静脉/肝脏迷走神经传入纤维，这表明顺铂的毒性作用涉及肠道而非肝脏传入纤维。(C) 2004 Elsevier B.V.版权所有
Cisplatin, a cancer chemotherapy agent, like many toxins, produces emesis and nausea. Abdominal vagotomy, or treatment with 57HT(3) receptor antagonists, blocks cisplatin-induced emesis, which suggests that it produces (albeit indirectly) activation of 5-HT3 receptors on vagal afferent fibers. Cisplatin induces a large release of intestinal 5-hydroxytryptamine (5-HT) that enters the hepatic portal vein, which may activate vagal afferent fibers in the portal vein or liver to induce emesis or other side effects of treatment (e.g., reduced food intake). This study was conducted to assess the effects of cisplatin on gastrointestinal and portal vein/liver vagal afferent fibers by recording the neurophysiological responses of the common hepatic branch (CHB) of the vagus in the rat. The CHB contains vagal afferent fibers that innervate the gastrointestinal (GI) tract, portal vein, and liver. Cisplatin (10 mg/kg; jugular vein, j.v.) produced an increase in multi-unit CHB activity and this effect was blocked by a 5-HT3-receptor antagonist (Y-25130, 0.8 mg, j.v.). Cutting the gastroduodenal branch (GDB), a sub-branch of the CHB that contains GI afferent fibers, resulted in a complete suppression of the multi-unit CHB discharge produced by cisplatin treatment. Single units that were cisplatin sensitive had their activity reduced by either 5-HT3 receptor antagonist treatment or cutting the GDB. Conversely, cisplatin insensitive units were not affected by 5-HT3-antagonism or GDB ablation. The present results indicate that cisplatin activates GI vagal afferent fibers via 5-HT3 receptors but does not affect portal vein/liver vagal afferent fibers, which indicates that intestinal but not hepatic afferent fibers are involved in the toxic effects of cisplatin. (C) 2004 Elsevier B.V. All rights reserved.