Pulmonary neuroepithelial bodies are polymodal airway sensors: Evidence for CO<sub>2</sub>/H<sup>+</sup>sensing

Pulmonary neuroepithelial bodies (NEB) in mammalian lungs are thought to function as airway O2sensors 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 Ca2+imaging method was used to assess CO2/H+-evoked changes in intracellular Ca2+. Exposure to 10 and 20% CO2or pH 6.8–7.2 evoked significant release of 5-HT with a distinct rise in intracellular Ca2+in hamster NEBs. This secretory response was dependent on the voltage-gated entry of extracellular Ca2+. 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.

Pulmonary neuroepithelial bodies are polymodal airway sensors: Evidence for CO₂/H⁺sensing Journal Articles