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Comment
. 2007 Apr 15;580(Pt. 2):359-60.
doi: 10.1113/jphysiol.2007.131805. Epub 2007 Mar 15.

Extracellular autocrine nucleotide signalling in a microenvironment: integrative physiology in a minute volume of airway surface liquid

Erik M Schwiebert  1
Affiliations
Comment

Extracellular autocrine nucleotide signalling in a microenvironment: integrative physiology in a minute volume of airway surface liquid

Erik M Schwiebert. J Physiol. .
No abstract available

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Figures

Figure 1
Figure 1. Cartoon depicting control of airway surface liquid via the integrative function of anion, cation and water transport and the local release of nucleotides and nucleosides with cyclic stress, phasic motion and other appropriate mechanostimuli
Wild-type CFTR is processed normally through the ER and Golgi to the ciliated apical membrane of airway surface epithelia (left). delF508-CFTR is retained in the ER due to a folding anomaly caused by a single phenylalanine deletion in a segment of the polypeptide that connects TMD1 and NBD1. This mutation occurs in approximately 70% of affected CF patients and on 90% of CFTR alleles (centre and right). In the normal physiology, there is a balance of NaCl and water transport governed in part by CFTR that sets proper ASL depth (left). In most CF, Cl− secretion is mostly lost due to retention of CFTR, and Na+ absorption (mainly due to ENaC) becomes hyperactive. As a result, water is absorbed too vigorously in CF due to osmotic forces. Dehydration of the airway surface liquid (centre) causes a ‘domino effect’ of problems with ciliary beat, mucociliary clearance, accumulation of dehydrated mucus and infection with opportunistic bacteria. The green and orange colour depicts non-mucoid and mucoid Pseudomonas aeruginosa bacteria accumulating within the thickened mucus in progressing CF disease. With the novel and different mechanical stimuli applied by Button, Picher, and Boucher in this and other studies, stimulation of secretion and enhancement of levels of nucleotides (ATP) and nucleosides (adenosine, Ado) inhibit ENaC-mediated Na+ hyperabsorption and rescue Cl− secretion through ‘rescue Cl− channels’ independent of CFTR that are expressed by airway and other epithelia.
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References

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