Loperamide Inhibits Tachykinin NK3-Receptor-Triggered Serotonin Release Without Affecting NK2-Receptor-Triggered Serotonin Release From Guinea Pig Colonic Mucosa
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...
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doaj-e261fe01ccbf46ae910e6072574218b92020-11-25T01:20:32ZengElsevierJournal of Pharmacological Sciences1347-86132005-01-01982175180Loperamide Inhibits Tachykinin NK3-Receptor-Triggered Serotonin Release Without Affecting NK2-Receptor-Triggered Serotonin Release From Guinea Pig Colonic MucosaShu-ichi Kojima0Masashi Ikeda1Yuichiro Kamikawa2Department of Pharmacology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan; Corresponding author. FAX: +81-282-86-2915 E-mail: s-kojima@dokkyomed.ac.jpInstitute of Medical Science, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, JapanDepartment of Pharmacology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, JapanThe 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 receptorhttp://www.sciencedirect.com/science/article/pii/S1347861319321966 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shu-ichi Kojima Masashi Ikeda Yuichiro Kamikawa |
spellingShingle |
Shu-ichi Kojima Masashi Ikeda Yuichiro Kamikawa Loperamide Inhibits Tachykinin NK3-Receptor-Triggered Serotonin Release Without Affecting NK2-Receptor-Triggered Serotonin Release From Guinea Pig Colonic Mucosa Journal of Pharmacological Sciences |
author_facet |
Shu-ichi Kojima Masashi Ikeda Yuichiro Kamikawa |
author_sort |
Shu-ichi Kojima |
title |
Loperamide Inhibits Tachykinin NK3-Receptor-Triggered Serotonin Release Without Affecting NK2-Receptor-Triggered Serotonin Release From Guinea Pig Colonic Mucosa |
title_short |
Loperamide Inhibits Tachykinin NK3-Receptor-Triggered Serotonin Release Without Affecting NK2-Receptor-Triggered Serotonin Release From Guinea Pig Colonic Mucosa |
title_full |
Loperamide Inhibits Tachykinin NK3-Receptor-Triggered Serotonin Release Without Affecting NK2-Receptor-Triggered Serotonin Release From Guinea Pig Colonic Mucosa |
title_fullStr |
Loperamide Inhibits Tachykinin NK3-Receptor-Triggered Serotonin Release Without Affecting NK2-Receptor-Triggered Serotonin Release From Guinea Pig Colonic Mucosa |
title_full_unstemmed |
Loperamide Inhibits Tachykinin NK3-Receptor-Triggered Serotonin Release Without Affecting NK2-Receptor-Triggered Serotonin Release From Guinea Pig Colonic Mucosa |
title_sort |
loperamide inhibits tachykinin nk3-receptor-triggered serotonin release without affecting nk2-receptor-triggered serotonin release from guinea pig colonic mucosa |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2005-01-01 |
description |
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 |
url |
http://www.sciencedirect.com/science/article/pii/S1347861319321966 |
work_keys_str_mv |
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