2. Academic Validation
  3. Investigation of 5-HT3 receptor-triggered serotonin release from guinea-pig isolated colonic mucosa: a role of PYY-containing endocrine cell

Investigation of 5-HT3 receptor-triggered serotonin release from guinea-pig isolated colonic mucosa: a role of PYY-containing endocrine cell

  • Eur J Pharmacol. 2017 Mar 15:799:196-200. doi: 10.1016/j.ejphar.2017.02.011.
Shu-Ichi Kojima 1,  Ken Kojima 2,  Tomoe Fujita 2
Affiliations

Affiliations

  • 1 Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu, Tochigi 321-0293, Japan. Electronic address: s-kojima@dokkyomed.ac.jp.
  • 2 Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu, Tochigi 321-0293, Japan.
PMID: 28189582 DOI: 10.1016/j.ejphar.2017.02.011
Abstract

The effect of a 5-HT3 receptor-selective agonist SR57227A was investigated on the outflow of 5-hydroxytryptamine (5-HT) from isolated muscle layer-free mucosal preparations of guinea-pig colon. The mucosal preparations were incubated in vitro and the outflow of 5-HT from these preparations was determined by high-performance liquid chromatography with electrochemical detection. SR57227A (100μM) produced a tetrodotoxin-resistant and sustained increase in the outflow of 5-HT from the mucosal preparations. The SR57227A-evoked sustained 5-HT outflow was completely inhibited by the 5-HT3 receptor antagonist ramosetron (1μM). The neuropeptide Y1 receptor antagonist BIBO3304 (100nM) partially inhibited the SR57227A-evoked sustained 5-HT outflow, but the Y2 receptor antagonist BIIE0246 (1μM) or the glucagon-like peptide-1 (GLP-1) receptor antagonist exendin-(9-39) (1μM), showed a minimal effect on the SR57227A-evoked sustained 5-HT outflow. In the presence of BIBO3304 (100nM) and exendin-(9-39) (1μM), SR57227A (100μM) failed to produce a sustained increase in the outflow of 5-HT. The Y1 receptor agonist [Leu31, Pro34]-neuropeptide Y (10nM), but not GLP-1-(7-36) amide (100nM), produced a sustained increase in the outflow of 5-HT. We found that 5-HT3 receptor-triggered 5-HT release from guinea-pig colonic mucosa is mediated by the activation of 5-HT3 receptors located at endocrine cells (enterochromaffin cells and peptide YY (PYY)-containing endocrine cells). The activation of both Y1 and GLP-1 receptors appears to be required for the maintenance of 5-HT3 receptor-triggered 5-HT release. It is therefore considered that 5-HT3 receptors located at colonic mucosa play a crucial role in paracrine signaling between enterochromaffin cells and PYY-containing endocrine cells.

Keywords

5-HT release; 5-HT(3) receptor; Colonic mucosa; Glucagon-like peptide-1; Neuropeptide Y(1) receptor; Peptide YY; SR57227A.

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