5-HT3 RECEPTOR ANTAGONISTS INJECTED INTO THE AREA POSTREMA INHIBIT CISPLATIN-INDUCED EMESIS IN THE FERRET
5-HT3 RECEPTOR ANTAGONISTS INJECTED INTO THE AREA POSTREMA INHIBIT CISPLATIN-INDUCED EMESIS IN THE FERRET
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DOI：
10.1111/j.1476-5381.1989.tb11948.x
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发表时间：
1989-05-01
影响因子：
7.3
通讯作者：
TYERS, MB
中科院分区：
文献类型：
--
作者：
HIGGINS, GA;KILPATRICK, GJ;TYERS, MB
本研究的目的是确定和调查的作用，5-羟色胺3（5-HT 3）受体在最后区的控制顺铂引起的雪貂呕吐。使用高亲和力5-HT 3受体配体[3 H]-GR 65630的匀浆结合和放射自显影实验鉴定了雪貂最后区中高浓度5-HT 3受体的存在。5-HT 3受体拮抗剂GR 38032 F、GR 65630 A和MDL 72222分别以1、0.1和1 mg kg-1剂量腹腔注射抑制顺铂（9 mg kg-1）诱导的呕吐。呕吐。使用的剂量范围是：GR 38032 F，0.01-1 μ g; GR 65630 A，0.001-0.1 μ g; MDL 72222，0.1-10 μ g。将酮色林（30 μ g）或甲硫替平（30.www.example.com）不连续注射到最后区中不能抑制顺铂诱导的呕吐。mu.gg将5-HT 3受体激动剂2-甲基-5-HT直接注射到最后区产生不完全的呕吐反应。这些结果证实了5-HT，特别是5-HT 3受体在控制顺铂诱导的呕吐中的作用，并表明这些受体在调节呕吐反应中的至少一个功能位点是最后区，即化学感受器触发区的位点。
The purpose of the present study was to identify and investigate the role of 5-hydroxytryptamine3 (5-HT3) receptors in the area postrema in the control of cisplatin-induced emesis in the ferret. Homogenate binding and autoradiography experiments using the high affinity 5-HT3 receptor ligand, [3H]-GR65630, identified the presence of a high concentration of 5-HT3 receptors in the area postrema of the ferret. Intraperitonal injection of the 5-HT3 receptor antagonists, GR38032F, GR65630A and MDL72222, at does of 1, 0.1 and 1 mg kg-1 respectively, inhibited emesis induced by cisplatin, 9 mg kg-1 i.p. Discrete injection of low doses of the 5-HT3 receptor antagonists directly into the area postrema region also inhibited cisplatin-induced (9 mg kg-1 i.p.) emesis. The dose ranges used were: GR38032F, 0.01-1 .mu.g; GR65630A, 0.001-0.1 .mu.g; MDL72222, 0.1-10 .mu.g. Cisplatin-induced emesis was not inhibited by discrete injection of ketanserin (30 .mu.g) or methiothepin (30 .mu.gg) into the area postrema. Injection of the 5-HT3 receptor agonist, 2-methyl-5-HT, directly into the area postrema produced an incomplete emetic response. These results confirm a role of 5-HT, and in particular 5-HT3 receptors, in the control of cisplatin-induced emesis, and show that at least one functional site for these receptors in modulating the emetic response is the area postrema, the locus of the chemoreceptor trigger zone.