title: Mast cell expression of the serotonin1A receptor in guinea pig and human intestine.
abstract: Serotonin [5-hydroxytryptamine (5-HT)] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells in the small intestine and action of 5-HT to degranulate the mast cells and release histamine in guinea pig small intestine and segments of human jejunum discarded during Roux-en-Y gastric bypass surgeries. Mast cells in human and guinea pig preparations expressed the 5-HT1A receptor. ELISA detected spontaneous release of histamine in guinea pig and human preparations. The selective 5-HT1A receptor agonist 8-hydroxy-PIPAT evoked release of histamine. A selective 5-HT1A receptor antagonist, WAY-100135, suppressed stimulation of histamine release by 5-HT or 8-hydroxy-PIPAT. Mast cell-stabilizing drugs, doxantrazole and cromolyn sodium, suppressed the release of histamine evoked by 5-HT or 8-hydroxy-PIPAT in guinea pig and human preparations. Our results support the hypothesis that serotonergic degranulation of enteric mast cells and release of preformed mediators, including histamine, are mediated by the 5-HT1A serotonergic receptor. Association of 5-HT with the pathophysiology of functional gastrointestinal disorders (e.g., irritable bowel syndrome) underlies a question of whether selective 5-HT1A receptor antagonists might have therapeutic application in disorders of this nature.
authors.affiliation: Dept. of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State Univ., 304 Hamilton Hall, 1645 Neil Ave., Columbus, OH 43210, USA.
authors.forename: Guo-Du
authors.initials: GD
authors.lastname: Wang
authors.forename: Xi-Yu
authors.initials: XY
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.forename: Meihua
authors.initials: M
authors.lastname: Qu
authors.forename: Sumei
authors.initials: S
authors.lastname: Liu
authors.forename: Guijun
authors.initials: G
authors.lastname: Fei
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Needleman
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Mikami
authors.forename: Jackie D
authors.initials: JD
authors.lastname: Wood
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004205:Cromolyn Sodium / Q000494:pharmacology; D017615:Enteric Nervous System / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013892:Thioxanthenes / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D006634:Histamine H1 Antagonists; D007202:Indicators and Reagents; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D012702:Serotonin Antagonists; D013892:Thioxanthenes; D044004:Xanthones; D044282:Receptor, Serotonin, 5-HT1A; C081293:WAY 100135; D003189:p-Methoxy-N-methylphenethylamine; D013779:Tetrodotoxin; D004205:Cromolyn Sodium; C010134:doxantrazole; D007665:Ketotifen
keywords: enteric mast cells; enteric nervous system; functional gastrointestinal disorders; histamine; irritable bowel syndrome