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A role for endogenous peptide YY in tachykinin NK 2 receptor‐triggered 5‐HT release from guinea pig isolated colonic mucosa
Author(s) -
Kojima Shuichi,
Tohei Atsushi,
Anzai Naohiko
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2012.02094.x
Subject(s) - peptide yy , endocrinology , agonist , medicine , receptor , tachykinin receptor , intestinal mucosa , guinea pig , chemistry , substance p , receptor antagonist , biology , antagonist , neuropeptide y receptor , neuropeptide
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 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. CONCLUSION AND IMPLICATIONS 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.