title: Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium.
abstract: BACKGROUND
  Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation.
  
  
  RESULTS
  Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells.
  
  
  CONCLUSIONS
  Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.
authors.affiliation: Department of Molecular Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
authors.forename: Ruth
authors.initials: R
authors.lastname: Dooley
authors.forename: Anastasia
authors.initials: A
authors.lastname: Mashukova
authors.forename: Bastian
authors.initials: B
authors.lastname: Toetter
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
authors.forename: Eva M
authors.initials: EM
authors.lastname: Neuhaus
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism*; D002478:Cells, Cultured; D051379:Mice; D009812:Odorants; D009831:Olfactory Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D058914:Purinergic Antagonists / Q000494:pharmacology*; D018035:Receptors, Odorant / Q000378:metabolism*; D012903:Smell / Q000187:drug effects / Q000502:physiology*
chemical_list: D058914:Purinergic Antagonists; D018035:Receptors, Odorant; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse