title: Pulmonary neuroepithelial bodies are polymodal airway sensors: evidence for CO2/H+ sensing.
abstract: Pulmonary neuroepithelial bodies (NEB) in mammalian lungs are thought to function as airway O2 sensors that release serotonin (5-HT) in response to hypoxia. Direct evidence that NEB cells also respond to airway hypercapnia/acidosis (CO2/H(+)) is presently lacking. We tested the effects of CO2/H(+) alone or in combination with hypoxia on 5-HT release from intact NEB cells in a neonatal hamster lung slice model. For the detection of 5-HT release we used carbon fiber amperometry. Fluorescence Ca(2+) imaging method was used to assess CO2/H(+)-evoked changes in intracellular Ca(2+). Exposure to 10 and 20% CO2 or pH 6.8-7.2 evoked significant release of 5-HT with a distinct rise in intracellular Ca(2+) in hamster NEBs. This secretory response was dependent on the voltage-gated entry of extracellular Ca(2+). Moreover, the combined effects of hypercapnia and hypoxia were additive. Critically, an inhibitor of carbonic anhydrase (CA), acetazolamide, suppressed CO2/H(+)-mediated 5-HT release. The expression of mRNAs for various CA isotypes, including CAII, was identified in NEB cells from human lung, and protein expression was confirmed by immunohistochemistry using a specific anti-CAII antibody on sections of human and hamster lung. Taken together our findings provide strong evidence for CO2/H(+) sensing by NEB cells and support their role as polymodal airway sensors with as yet to be defined functions under normal and disease conditions.
authors: Division of Pathology, Department of Paediatric Laboratory Medicine, The Research Institute, The Hospital for Sick Children and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; and.
authors: S
authors: S
authors: Livermore
authors: Division of Pathology, Department of Paediatric Laboratory Medicine, The Research Institute, The Hospital for Sick Children and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; and.
authors: Y
authors: Y
authors: Zhou
authors: Division of Pathology, Department of Paediatric Laboratory Medicine, The Research Institute, The Hospital for Sick Children and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; and.
authors: J
authors: J
authors: Pan
authors: Division of Pathology, Department of Paediatric Laboratory Medicine, The Research Institute, The Hospital for Sick Children and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; and.
authors: H
authors: H
authors: Yeger
authors: Department of Biology, McMaster University, Hamilton, Ontario, Canada.
authors: C A
authors: CA
authors: Nurse
authors: Division of Pathology, Department of Paediatric Laboratory Medicine, The Research Institute, The Hospital for Sick Children and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; and ernest.cutz@sickkids.ca.
authors: E
authors: E
authors: Cutz
mesh_terms: D000136:Acid-Base Equilibrium; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology / Q000502:physiology*; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism; D002648:Child; D006224:Cricetinae; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D008168:Lung / Q000166:cytology; D046568:Neuroepithelial Bodies / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism
chemical_list: D002245:Carbon Dioxide; D012701:Serotonin; D002256:Carbonic Anhydrases
keywords: chemosensing; serotonin