Melatonin inhibits tachykinin NK? receptor-triggered 5-HT release from guinea pig isolated colonic mucosa.

ABSTRACT:

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? receptor-selective agonist, [?-Ala?]-neurokinin A(4-10) [?Ala-NKA-(4-10)] can induce 5-HT release from guinea pig colonic mucosa via NK? 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? receptor agonist, ?Ala-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 ?Ala-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? receptor agonist, 5-methoxycarbonylamino-N-acetyltryptamine mimicked the inhibitory effect of melatonin on ?Ala-NKA-(4-10)-evoked 5-HT outflow. A MT? 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?/MT? receptor antagonist luzindole, nor a MT? receptor antagonist N-pentanoyl-2-benzyltryptamine modified the concentration-response curve to melatonin.

Conclusions and implications

Melatonin inhibits NK? receptor-triggered 5-HT release from guinea pig colonic mucosa by acting at a MT? melatonin receptor located directly on the mucosal layer, without affecting 5-HT degradation processes. Possible contributions of MT?/MT? 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.

SUBMITTER: Kojima S 

PROVIDER: S-EPMC3051389 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature