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Melatonin inhibits tachykinin NK 2 receptor‐triggered 5‐HT release from guinea pig isolated colonic mucosa
Author(s) -
Kojima Shuichi,
Tohei Atsushi,
Ikeda Masashi
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.01122.x
Subject(s) - melatonin , agonist , endocrinology , medicine , luzindole , receptor , tachykinin receptor , receptor antagonist , melatonin receptor , neurokinin a , chemistry , biology , antagonist , substance p , neuropeptide
BACKGROUND AND PURPOSE Melatonin is involved in the regulation of colonic motility, and sensation, but little is known about the influence of melatonin on 5‐hydroxytryptamine (5‐HT) release from colonic mucosa. A tachykinin NK 2 receptor‐selective agonist, [β‐Ala 8 ]‐neurokinin A 4‐10 [βAla‐NKA‐(4‐10)] can induce 5‐HT release from guinea pig colonic mucosa via NK 2 receptors on the mucosal layer. The present study was designed to determine the influence of melatonin on 5‐HT release from guinea pig colonic mucosa, evoked by the NK 2 receptor agonist, βAla‐NKA‐(4‐10). EXPERIMENTAL APPROACH The effect of melatonin was investigated on the outflow of 5‐HT and its metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) from muscle layer‐free mucosal preparations of guinea pig colon, using high‐performance liquid chromatography with electrochemical detection. KEY RESULTS Melatonin caused a sustained decline in the βAla‐NKA‐(4‐10)‐evoked 5‐HT outflow from the muscle layer‐free mucosal preparations, but failed to affect its metabolite 5‐HIAA outflow. The specific MT 3 receptor agonist, 5‐methoxycarbonylamino‐N‐acetyltryptamine mimicked the inhibitory effect of melatonin on βAla‐NKA‐(4‐10)‐evoked 5‐HT outflow. A MT 3 receptor antagonist prazosin shifted the concentration‐response curve of melatonin to the right in a concentration‐dependent manner and depressed the maximum effect, but neither a combined MT 1 /MT 2 receptor antagonist luzindole, nor a MT 2 receptor antagonist N‐pentanoyl‐2‐benzyltryptamine modified the concentration–response curve to melatonin. CONCLUSIONS AND IMPLICATIONS Melatonin inhibits NK 2 receptor‐triggered 5‐HT release from guinea pig colonic mucosa by acting at a MT 3 melatonin receptor located directly on the mucosal layer, without affecting 5‐HT degradation processes. Possible contributions of MT 1 /MT 2 melatonin receptors to the inhibitory effect of melatonin appear to be negligible. Melatonin may act as a modulator of excess 5‐HT release from colonic mucosa.