British Journal of Pharmacology 2012-11-01

A role for endogenous peptide YY in tachykinin NK(2) receptor-triggered 5-HT release from guinea pig isolated colonic mucosa.

Shu-ichi Kojima, Atsushi Tohei, Naohiko Anzai

Index: Br. J. Pharmacol. 167(6) , 1362-8, (2012)

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Abstract

The colon-derived peptide hormone, peptide YY (PYY), regulates colonic motility, secretion and postprandial satiety; but little is known about the influence of endogenous PYY on 5-HT release from colonic mucosa. Tachykinin NK(2) receptor-selective agonist, βAla-NKA-(4-10) induces 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 endogenous PYY on 5-HT release from guinea pig colonic mucosa, evoked by the NK(2) receptor agonist, βAla-NKA-(4-10).Muscle layer-free mucosal preparations of guinea pig colon were incubated in vitro and the outflow of PYY or 5-HT and its metabolite, 5-HIAA, from these preparations were determined by enzyme immunoassays or HPLC with electrochemical detection respectively.βAla-NKA-(4-10) produced a tetrodotoxin-resistant sustained increase in the outflow of PYY and 5-HT from the mucosal preparations. The βAla-NKA-(4-10)-evoked 5-HT outflow was partially inhibited by Y(1) receptor antagonist, BIBO3304, and Y(2) receptor antagonist, BIIE0246, but with less potency. Exogenously-applied PYY also produced a sustained increase in the outflow of 5-HT that was inhibited by Y(1) blockade but not Y(2) blockade.Our findings support the view that the NK(2) receptor-selective agonist, βAla-NKA-(4-10) produces a long-lasting PYY release from guinea pig colonic mucosa via NK(2) receptors on L cells and βAla-NKA-(4-10)-evoked 5-HT release is in part mediated by endogenously released PYY, acting mainly on Y(1) receptors on EC cells. The PYY-containing L cells appear to play a role in controlling the release of 5-HT from colonic EC cells.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.