title: Role of histamine and its receptor subtypes in stimulation of conjunctival goblet cell secretion.
abstract: OBJECTIVE
  The purpose of this study was to determine the effect of histamine and its receptors on goblet cell secretion.
  
  
  METHODS
  Cultured rat and human goblet cells were grown in RPMI 1640. Goblet cell secretion of high molecular weight glycoconjugate was measured by an enzyme-linked lectin assay. Cultured rat goblet cells were homogenized and either RNA was isolated for RT-PCR or proteins were isolated for Western blot analysis for presence of histamine receptors subtypes H₁ through H₄. The localization of these receptors was determined in rat and human goblet cells by immunofluorescence microscopy.
  
  
  RESULTS
  Histamine stimulated goblet cell secretion in a concentration- and time-dependent manner. All four histamine receptors were present in cultured rat and human goblet cells. Use of agonists specific to individual histamine receptor subtypes indicated that the rank order of agonist stimulation was H₁ = H₃ > H₄ > H₂. Using antagonists specific to individual histamine receptor subtypes determined that H₂ and H₃, but not the H₁ and H₄, antagonists, inhibited histamine-stimulated conjunctival goblet cell secretion.
  
  
  CONCLUSIONS
  Rat and human conjunctival goblet cells are a direct target of histamine, which induces secretion. All four histamine receptors are present in rat and human conjunctiva and are active in rat conjunctival goblet cells. These findings suggest that all four histamine receptor subtypes are important for conjunctival goblet cell secretion. Blockage of histamine receptor subtypes could prevent the excess mucus production associated with ocular allergy.
authors.affiliation: Department of Ophthalmology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Densen
authors.initials: D
authors.lastname: Hayashi
authors.forename: Dayu
authors.initials: D
authors.lastname: Li
authors.forename: Chisato
authors.initials: C
authors.lastname: Hayashi
authors.forename: Marie
authors.initials: M
authors.lastname: Shatos
authors.forename: Robin R
authors.initials: RR
authors.lastname: Hodges
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Dartt
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002927:Cimetidine / Q000494:pharmacology; D003228:Conjunctiva / Q000166:cytology* / Q000378:metabolism; D003233:Conjunctivitis, Allergic / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D020397:Goblet Cells / Q000378:metabolism*; D006632:Histamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011968:Receptors, Histamine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C092716:2-(3-trifluoromethylphenyl)histamine; D017442:Histamine Agonists; D006633:Histamine Antagonists; D007211:Indoles; D008761:Methylhistamines; D010879:Piperazines; D012333:RNA, Messenger; D011968:Receptors, Histamine; D013844:Thiazoles; C076207:amthamine; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; C025566:4-methylhistamine; D002927:Cimetidine; D006632:Histamine