Adenosine‐evoked Na+transport in human airway epithelial cells

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Abstract
Background and purpose: Absorptive epithelia express apical receptors that allow nucleotides to inhibit Na+transport but ATP unexpectedly stimulated this process in an absorptive cell line derived from human bronchiolar epithelium (H441 cells) whilst UTP consistently caused inhibition. We have therefore examined the pharmacological basis of this anomalous effect of ATP.Experimental approach: H441 cells were grown on membranes and the short circuit current (ISC) measured in Ussing chambers. In some experiments, [Ca2+]iwas measured fluorimetrically using Fura ‐2. mRNAs for adenosine receptors were determined by the polymerase chain reaction (PCR).Key results: Cross desensitization experiments showed that the inhibitory response to UTP was abolished by prior exposure to ATP whilst the stimulatory response to ATP persisted in UTP‐pre‐stimulated cells. Apical adenosine evoked an increase inISCand this response resembled the stimulatory component of the response to ATP, and could be mimicked by adenosine receptor agonists. Pre‐stimulation with adenosine abolished the stimulatory component of the response to ATP. mRNA encoding A1, A2Aand A2Breceptor subtypes, but not the A3subtype, was detected in H441 cells and adenosine receptor antagonists could abolish the ATP‐evoked stimulation of Na+absorption.Conclusions and implications: The ATP‐induced stimulation of Na+absorption seems to be mediated via A2A/Breceptors activated by adenosine produced from the extracellular hydrolysis of ATP. The present data thus provide the first description of adenosine‐evoked Na+transport in airway epithelial cells and reveal a previously undocumented aspect of the control of this physiologically important ion transport process.British Journal of Pharmacology(2006)149, 43–55. doi:10.1038/sj.bjp.0706822