[Pharmacology of ion channels in mucoviscidosis. Physiological bases and therapeutic applications].
Phenotypical expression of cystic fibrosis (CF) includes decreased epithelial chloride secretion and increased sodium absorption. These anomalies produce increased water absorption and a dehydrated mucus responsible for decreased mucociliary clearance. Identification of the gene responsible for the genetic disease (CFTR for cystic fibrosis transmembrane conductance regulator) together with a more accurate comprehension of complexes interactions that exist between the CFTR gene product and other epithelial ionic channels has created novel opportunities for discovering specific pharmacological drugs to treat the disease. Amiloride, which limits sodium hyperabsorption, has demonstrated both efficacy and safety in vivo in a restricted number of adult patients. Nucleotides such as ATP or UTP, prescribed in association with amiloride, increase chloride secretion. Potassium channel openers, by stimulating transepithelial chloride transport, may represent an additional innovative approach. Specific pharmacology to CF is not competitive but rather complementary to gene therapy.
Danner
I
I
Laboratoire de Physiopathologie et Pharmacologie Cellulaire et Moléculaire G & R Laënnec, Hôpital G & R Laënnec, Nantes.
Baro-Puigdemasa
I
I
Escande
D
D
D000255:Adenosine Triphosphate / Q000502:physiology; D000293:Adolescent; D000328:Adult; D000584:Amiloride / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000502:physiology; D003550:Cystic Fibrosis / Q000235:genetics / Q000503:physiopathology*; D004848:Epithelium / Q000502:physiology; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D015221:Potassium Channels / Q000502:physiology; D012137:Respiratory System / Q000166:cytology; D015222:Sodium Channels / Q000502:physiology
D018118:Chloride Channels; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; D000584:Amiloride; D000255:Adenosine Triphosphate
Pharmacologie des canaux ioniques dans la mucoviscidose. Bases physiologiques et applications thérapeutiques.