title: Investigation of 5-HT3receptor-triggered serotonin release from guinea-pig isolated colonic mucosa: a role of PYY-containing endocrine cell.
abstract: The effect of a 5-HT3receptor-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-HT3receptor antagonist ramosetron (1μM). The neuropeptide Y1receptor antagonist BIBO3304 (100nM) partially inhibited the SR57227A-evoked sustained 5-HT outflow, but the Y2receptor 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 Y1receptor 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-HT3receptor-triggered 5-HT release from guinea-pig colonic mucosa is mediated by the activation of 5-HT3receptors located at endocrine cells (enterochromaffin cells and peptide YY (PYY)-containing endocrine cells). The activation of both Y1and GLP-1 receptors appears to be required for the maintenance of 5-HT3receptor-triggered 5-HT release. It is therefore considered that 5-HT3receptors located at colonic mucosa play a crucial role in paracrine signaling between enterochromaffin cells and PYY-containing endocrine cells.
authors.affiliation: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu, Tochigi 321-0293, Japan. Electronic address: s-kojima@dokkyomed.ac.jp.
authors.forename: Shu-Ichi
authors.initials: SI
authors.lastname: Kojima
authors.affiliation: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu, Tochigi 321-0293, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kojima
authors.affiliation: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu, Tochigi 321-0293, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000818:Animals; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055098:Endocrine Cells / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019894:Peptide YY / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology
chemical_list: D010880:Piperidines; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D019894:Peptide YY; D012701:Serotonin; C083009:4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride
keywords: 5-HT release; 5-HT(3) receptor; Colonic mucosa; Glucagon-like peptide-1; Neuropeptide Y(1) receptor; Peptide YY; SR57227A