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

• Main Authors: Shu-ichi Kojima, Masashi Ikeda, Yuichiro Kamikawa
• Format: Article
• Language: English
• Published: Elsevier 2005-01-01
• Series: Journal of Pharmacological Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S1347861319321966

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. Keywords:: colon, serotonin, loperamide, tachykinin, opioid receptor