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Article Dans Une Revue Journal of Cystic Fibrosis Année : 2008

Stimulation of salivary secretion in vivo by CFTR potentiators in Cftr+/+ and Cftr−/− mice

Résumé

Physiologically, salivary secretion is controlled by cholinergic and adrenergic pathways but the role of ionic channels in this process is not yet clearly understood. In cystic fibrosis (CF), most exocrine glands failed to response to β-adrenergic agonists. Methods To determine the implication of CFTR in this process, we measured in vivo the salivary secretion of Cftr+/+ and Cftr−/− mice in the presence of 2 water-soluble benzo[c]quinolizinium derivatives; MPB-07 a potentiator of CFTR Cl− channel and MPB-05 an inactive analogue. We also used genistein and its vehicle ethanol to confirm the implication of CFTR in salivary secretion. Results We showed that subcutaneous injection of MPB-07 in the mice cheek enhanced in a dose dependent manner the isoprenaline-induced salivary secretion in Cftr+/+ but not in Cftr−/− mice. By contrast, MPB-05 did not activate the salivary secretion in Cftr+/+ mice. The CFTR activator genistein (50 μM) significantly potentiated the secretory response of Cftr+/+ mice whereas its vehicle, ethanol, had no effect. Conclusions These results show for the first time in vivo pharmacological stimulation of salivary secretion by a water-soluble CFTR potentiator, MPB-07 and by the isoflavone, ethanol-soluble genistein and suggest that this chloride channel plays an important role in salivary gland physiology.

Dates et versions

hal-00402063 , version 1 (06-07-2009)

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Sabrina Noël, Pierre-Olivier Strale, Luc Dannhoffer, Martina Wilke, Hugo Dejonge, et al.. Stimulation of salivary secretion in vivo by CFTR potentiators in Cftr+/+ and Cftr−/− mice. Journal of Cystic Fibrosis, 2008, 7 (2), pp.128-133. ⟨10.1016/j.jcf.2007.06.005⟩. ⟨hal-00402063⟩
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