Background and purpose
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). Experimental approach: 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. Key
Purpose
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). Experimental approach: 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. Key
Results
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.