Stimulation of salivary secretion in vivo by CFTR potentiators in Cftr+/+ and Cftr−/− mice
Copyright policy )Stimulation of salivary secretion in vivo by CFTR potentiators in Cftr+/+ and Cftr−/− mice
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 beta-adrenergic agonists.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.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 microM) significantly potentiated the secretory response of Cftr(+/+) mice whereas its vehicle, ethanol, had no effect.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.
- French National Centre for Scientific Research France
- University of Poitiers France
- UNIVERSITE DE POITIERS France
- Erasmus University Medical Center Netherlands
- Erasmus University Rotterdam Netherlands
Pulmonary and Respiratory Medicine, Mice, Knockout, Cystic Fibrosis, Salivary secretion, Benzoquinolizinium, Cystic Fibrosis Transmembrane Conductance Regulator, Genistein, Salivary Glands, Quaternary Ammonium Compounds, Disease Models, Animal, Mice, EMC MGC-02-21-02, Animals, Mice, Inbred CFTR, Female, Pediatrics, Perinatology, and Child Health, CFTR, Saliva, Protein Kinase Inhibitors, Quinolizines, Knockout mice
Pulmonary and Respiratory Medicine, Mice, Knockout, Cystic Fibrosis, Salivary secretion, Benzoquinolizinium, Cystic Fibrosis Transmembrane Conductance Regulator, Genistein, Salivary Glands, Quaternary Ammonium Compounds, Disease Models, Animal, Mice, EMC MGC-02-21-02, Animals, Mice, Inbred CFTR, Female, Pediatrics, Perinatology, and Child Health, CFTR, Saliva, Protein Kinase Inhibitors, Quinolizines, Knockout mice
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