Loperamide Inhibits Tachykinin NK3-Receptor-Triggered Serotonin Release Without Affecting NK2-Receptor-Triggered Serotonin Release From Guinea Pig Colonic Mucosa
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- Kojima Shu-ichi
- Department of Pharmacology, Dokkyo University School of Medicine
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- Ikeda Masashi
- Institute of Medical Science, Dokkyo University School of Medicine
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- Kamikawa Yuichiro
- Department of Pharmacology, Dokkyo University School of Medicine
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Abstract
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 A4-10 (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>
Journal
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 98 (2), 175-180, 2005
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390001205175741568
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- NII Article ID
- 10025728508
- 130000074309
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- NII Book ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL BIB ID
- 7337909
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- PubMed
- 15942125
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed