Reserpine inhibits CFTR chloride channel in Caco-2 monolayers

Secretory diarrhoea continues to be an enormous health problem worldwide. Pharmacological block of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is regarded as a potential therapeutic target for secretory diarrhoea. The main objective of this study was to determine the action of the plant derived compound, reserpine, on the CFTR chloride channel. The effect of reserpine on the CFTR chloride current was investigated using the short circuit current (Isc) technique on monolayers of Caco-2 cells grown on permeable supports. Monolayers had a transepithelial resistance (RT) of 467 ± 40 Ω/cm2 and an initial Isc of 4.5 ± 1.2 μA/cm2 (n=22). Initial experiments on intact Caco-2 monolayers suggested that a 15 min, apical preincubation with 50μM reserpine resulted in an inhibition of the 10 μM forskolin-stimulated Isc (n=3). All further experiments were carried out in nystatin-permeabilised Caco-2 monolayers. Basolateral addition of 10μM Forskolin resulted in a...