Fukui H, Yamamoto M, Sasaki S, Sato S
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Eur J Pharmacol. 1994 May 12;257(1-2):47-52. doi: 10.1016/0014-2999(94)90692-0.
The involvement of visceral afferent fibers and 5-HT3 or 5-HT4 receptors in the vomiting induced by oral administration of copper sulfate was investigated in beagle dogs. Vomiting induced by copper sulfate (100 mg/kg) was inhibited markedly by bilateral abdominal vagotomy and bilateral greater splanchnic nerve section. The vomiting induced by copper sulfate was inhibited by blocking 5-HT4 receptors with high doses (1 and 3 mg/kg, i.v.) of ICS 205-930. On the other hand, blocking 5-HT3 receptors with MDL 72222 (0.5 and 5 mg/kg, i.v.) or low doses (0.01 mg/kg i.v.) of ICS 205-930 had no apparent effect on the vomiting induced by copper sulfate. Oral administration of a 5-HT4 receptor agonist, 5-methoxytryptamine (5-MT), caused vomiting at a dose of 100 mg/kg, and the vomiting was inhibited markedly by abdominal visceral nerve section or a high dose (1 mg/kg, i.v.), but not a low dose (0.01 mg/kg, i.v.), of ICS 205-930. Intravenous administration of 5-MT (10 mg/kg) failed to induce vomiting. These results suggest that the abdominal visceral afferent fibers and possibly peripheral 5-HT4 receptors play an important role in the vomiting induced by oral administration of copper sulfate in dogs.
在比格犬中研究了内脏传入纤维以及5-HT3或5-HT4受体在口服硫酸铜诱发呕吐中的作用。双侧腹部迷走神经切断术和双侧内脏大神经切断术可显著抑制硫酸铜（100mg/kg）诱发的呕吐。高剂量（1和3mg/kg，静脉注射）的ICS 205-930阻断5-HT4受体可抑制硫酸铜诱发的呕吐。另一方面，MDL 72222（0.5和5mg/kg，静脉注射）或低剂量（0.01mg/kg静脉注射）的ICS 205-930阻断5-HT3受体对硫酸铜诱发的呕吐无明显影响。口服5-HT4受体激动剂5-甲氧基色胺（5-MT），剂量为100mg/kg时可引起呕吐，腹部内脏神经切断术或高剂量（1mg/kg，静脉注射）而非低剂量（0.01mg/kg，静脉注射）的ICS 205-930可显著抑制该呕吐。静脉注射5-MT（10mg/kg）未能诱发呕吐。这些结果表明，腹部内脏传入纤维以及可能的外周5-HT4受体在犬口服硫酸铜诱发的呕吐中起重要作用。
