Article date: March 2011
By: Shu‐ichi Kojima, Atsushi Tohei, Masashi Ikeda in Volume 162, Issue 5, pages 1179-1185
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 NK2 receptor‐selective agonist, [β‐Ala8]‐neurokinin A4‐10[βAla‐NKA‐(4‐10)] can induce 5‐HT release from guinea pig colonic mucosa via NK2 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 NK2 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 MT3 receptor agonist, 5‐methoxycarbonylamino‐N‐acetyltryptamine mimicked the inhibitory effect of melatonin on βAla‐NKA‐(4‐10)‐evoked 5‐HT outflow. A MT3 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 MT1/MT2 receptor antagonist luzindole, nor a MT2 receptor antagonist N‐pentanoyl‐2‐benzyltryptamine modified the concentration–response curve to melatonin.
CONCLUSIONS AND IMPLICATIONS Melatonin inhibits NK2 receptor‐triggered 5‐HT release from guinea pig colonic mucosa by acting at a MT3 melatonin receptor located directly on the mucosal layer, without affecting 5‐HT degradation processes. Possible contributions of MT1/MT2 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.
DOI: 10.1111/j.1476-5381.2010.01122.x
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