title: Histamine elevates free intracellular calcium in mouse retinal dopaminergic cells via H1-receptors.
abstract: OBJECTIVE
  Previously, retinopetal axons containing histamine and dopaminergic neurons expressing histamine H(1)-receptor had been localized in mouse retinas using anatomic techniques. The goal of these experiments was to demonstrate that these receptors are functional.
  
  
  METHODS
  Dopaminergic cells were acutely isolated from retinas of transgenic mice expressing red fluorescent protein under control of the tyrosine hydroxylase promoter and loaded with the calcium indicator Fura-2.
  
  
  RESULTS
  Under control conditions, there were spontaneous oscillations in the levels of free intracellular calcium in dopaminergic cells. These oscillations were abolished in nominally calcium-free extracellular medium and in 1 μM tetrodotoxin, findings suggesting that the oscillations were mediated by calcium entry across the plasma membrane in response to sodium-dependent action potentials. Histamine increased the mean free intracellular calcium in the dopaminergic cells by increasing the frequency and/or amplitude of the calcium oscillations. The effects of histamine were dose-dependent and reached maximum at 5 μM. With this dose, there was a 65% increase in the mean free intracellular calcium concentration. The histamine H(1)-receptor antagonist, pyrilamine, blocked the effects of 5 μM histamine when applied at 50 μM. The selective histamine H(1)-receptor agonists, 2-(3-trifluoromethylphenyl) histamine and methylhistaprodifen significantly increased mean free intracellular calcium when applied at 5 μM.
  
  
  CONCLUSIONS
  Histamine released from retinopetal axons in the mouse retina can elevate intracellular calcium levels in the perikarya of dopaminergic cells via the activation of histamine H(1)-receptors.
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Houston, Texas, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Frazão
authors.forename: Douglas G
authors.initials: DG
authors.lastname: McMahon
authors.forename: Walter
authors.initials: W
authors.lastname: Schunack
authors.forename: Proleta
authors.initials: P
authors.lastname: Datta
authors.forename: Ruth
authors.initials: R
authors.lastname: Heidelberger
authors.forename: David W
authors.initials: DW
authors.lastname: Marshak
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism
chemical_list: D017442:Histamine Agonists; D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D006632:Histamine; D002118:Calcium; D004298:Dopamine