Involvement of substance P in the development of cisplatin-induced acute and delayed pica in rats
Involvement of substance P in the development of cisplatin-induced acute and delayed pica in rats
复制标题
DOI：
10.1111/bph.12629
复制
发表时间：
2014-06-01
影响因子：
7.3
通讯作者：
Yamatodani, Atsushi
中科院分区：
文献类型：
--
作者：
Yamamoto, Kouichi;Asano, Keiko;Yamatodani, Atsushi
背景和目的虽然P物质（SP）和神经激肽NK1受体参与顺铂诱导的急性和延迟性呕吐，但它们的确切作用尚不清楚。异食癖，即大鼠食用非营养性物质，如高岭土，可以作为人类恶心的模型。我们研究了顺铂诱导异食癖的时间依赖性变化以及SP和NK1受体在这种行为中的参与。实验方法给大鼠顺铂，每天注射或不注射5- ht3受体拮抗剂（格拉司琼）或NK1受体拮抗剂（阿瑞匹坦），然后监测高岭土摄入量5天。通过体内脑微透析检测格拉司琼对顺铂诱导的主要编码SP的原肽激肽- a (pre - protachykinin- a, PPT-A) mRNA表达的影响，以及对SP在髓质释放的影响。关键结果铂在给药后8小时内诱发异食癖，持续5天。格拉司琼抑制异食症急性期（第1天），但不抑制延迟期（第2-5天），而阿瑞吡坦则消除这两个阶段。注射顺铂24h内，大鼠髓质中PPT-A mRNA表达及SP释放量均显著升高；这些结果在观察期间持续，并被格拉司琼抑制长达24小时。结论和意义顺铂诱导的大鼠异食癖的特征与顺铂诱导的人类呕吐的临床发现相似，我们发现髓质中SP的产生和NK1受体的激活参与了顺铂诱导的异食癖。
Background and PurposeAlthough substance P (SP) and neurokinin NK1 receptors have been reported to be involved in cisplatin-induced acute and delayed emesis, their precise roles remain unclear. Pica, the consumption of non-nutrient materials such as kaolin in rats, can be used as a model of nausea in humans. We investigated the time-dependent changes in cisplatin-induced pica and the involvement of SP and NK1 receptors in this behaviour.Experimental ApproachRats were administered cisplatin with or without a daily injection of a 5-HT3 receptor antagonist (granisetron) or an NK1 receptor antagonist (aprepitant), and kaolin intake was then monitored for 5 days. The effects of granisetron on the cisplatin-induced expression of preprotachykinin-A (PPT-A) mRNA, which encodes mainly for SP, and on SP release in the medulla, measured by in vivo brain microdialysis, were also investigated.Key ResultsCisplatin induced pica within 8h of its administration that continued for 5 days. Granisetron inhibited the acute phase (day 1), but not the delayed phase (days 2-5), of pica, whereas aprepitant abolished both phases. Within 24h of the injection of cisplatin, PPT-A mRNA expression and SP release in the medulla were significantly increased; these findings lasted during the observation period and were inhibited by granisetron for up to 24h.Conclusions and ImplicationsThe profiles of cisplatin-induced pica in rats are similar to clinical findings for cisplatin-induced emesis in humans, and we showed that SP production in the medulla and activation of NK1 receptors are involved in this cisplatin-induced pica.