title: A role for endogenous peptide YY in tachykinin NK(2)  receptor-triggered 5-HT release from guinea pig isolated colonic mucosa.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan. s-kojima@dokkyomed.ac.jp
authors: Shu-ichi
authors: S
authors: Kojima
authors: Atsushi
authors: A
authors: Tohei
authors: Naohiko
authors: N
authors: Anzai
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D019894:Peptide YY / Q000378:metabolism* / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D019894:Peptide YY; C064218:neurokinin A (4-10), beta-Ala(8)-; D012701:Serotonin; D015288:Neurokinin A