Loperamide Inhibits Tachykinin NK3-Receptor-Triggered Serotonin Release Without Affecting NK2-Receptor-Triggered Serotonin Release From Guinea Pig Colonic Mucosa

• Kojima Shu-ichi

  Department of Pharmacology, Dokkyo University School of Medicine

• Ikeda Masashi

  Institute of Medical Science, Dokkyo University School of Medicine

• Kamikawa Yuichiro

  Department of Pharmacology, Dokkyo University School of Medicine

抄録

The effect of loperamide on tachykinin NK₂- and NK₃-receptor-mediated 5-HT outflow from guinea pig colonic mucosa was investigated in vitro. The selective tachykinin NK₂-receptor agonist [β-Ala⁸]-neurokinin A_4-10 (βAla-NKA) or the selective NK₃-receptor agonist senktide elicited an increase in 5-HT outflow from whole colonic strips, but not from mucosa-free muscle layer preparations. The enhancing effect of βAla-NKA and senktide was prevented by the selective NK₂-receptor antagonist GR94800 or the selective NK₃-receptor antagonist SB222200. Loperamide concentration-dependently suppressed the senktide-evoked 5-HT outflow, but failed to affect the βAla-NKA-evoked 5-HT outflow. The κ-opioid receptor antagonist nor-binaltorphimine or the δ-opioid receptor antagonist naltrindole displaced the concentration-response curve for the suppressant action of loperamide to the right without significant depression of the maximum. However, the μ-opioid receptor antagonist CTOP did not affect the suppressant effect of loperamide. We concluded that the NK₃ receptor-triggered 5-HT release from colonic mucosa is suppressed by loperamide-sensitive mechanisms, whereas the NK₂-receptor-triggered 5-HT release is loperamide-insensitive. Our data also suggest that the suppressant effect of loperamide is probably mediated by the activation of κ- and δ-opioid receptors located on intrinsic neurons.<br>

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 98 (2), 175-180, 2005

  公益社団法人 日本薬理学会

キーワード

• colon
• serotonin
• loperamide
• tachykinin
• opioid receptor

詳細情報

• CRID: 1390001205175741568
• NII論文ID: 10025728508
• NII論文ID: 130000074309
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.fpj05011x
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 7337909
• PubMed: 15942125
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7337909
• Web Site: https://search.jamas.or.jp/link/ui/2006277943
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可