Adenosine-evoked Na+ transport in human airway epithelial cells.
OBJECTIVE
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.


METHODS
H441 cells were grown on membranes and the short circuit current (I(SC)) measured in Ussing chambers. In some experiments, [Ca(2+)](i) was measured fluorimetrically using Fura -2. mRNAs for adenosine receptors were determined by the polymerase chain reaction (PCR).


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 in I(SC) and 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 A(1), A(2A) and A(2B) receptor subtypes, but not the A(3) subtype, was detected in H441 cells and adenosine receptor antagonists could abolish the ATP-evoked stimulation of Na(+) absorption.


CONCLUSIONS
The ATP-induced stimulation of Na(+) absorption seems to be mediated via A(2A/B) receptors 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.
Chambers
L A
LA
Lung Membrane Transport Group, Division of Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
Constable
M
M
Clunes
M T
MT
Olver
R E
RE
Ko
W H
WH
Inglis
S K
SK
Wilson
S M
SM
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003627:Data Interpretation, Statistical; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D058915:Purinergic P1 Receptor Antagonists; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000187:drug effects; D058473:Receptors, Purinergic P2Y2; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism*
D005456:Fluorescent Dyes; C546385:P2RY2 protein, human; D058915:Purinergic P1 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C022571:adenosine 5'-O-(3-thiotriphosphate); D012313:RNA; D000255:Adenosine Triphosphate; D012964:Sodium; D000241:Adenosine; D002118:Calcium; D016257:Fura-2