Effects of insulin and tyrosine kinase inhibitor on ion transport in the alveolar cell of the fetal lung

Abstract We studied the effect of insulin and lavendustin-A (a tyrosine kinase inhibitor) on the short-circuit current (I SC ) of primary cultures of fetal distal rat lung epithelium (FDLE). Insulin (2μM) on the basolateral side of the monolayer increased I SC from 5.76±0.83μA/cm 2 (SEM, n=7) to 7.23±1.00μA/cm 2 (p 2 to 1.53±0.34μA/cm 2 (p SC with the insulin-induced increase in I SC in the absence of amiloride (1.47±0.22μA/cm 2 , n=7) being significantly larger than that in the presence of 10μM amiloride (0.53±0.14μA/cm 2 , n=4; p SC ; i.e., insulin increased I SC in lavendustin-A treated monolayers (0.63±0.09μA/cm 2 , n=5; p SC (change in I SC = 0.04±0.03μA/cm 2 , n=6), suggesting that lavendustin-A had blocked the insulin's effect on the amiloride-insensitive I SC . Lavendustin-A (10 μM) had no significant effect on the basal I SC in control and amiloride treated monolayers. Our studies demonstrate that insulin increases amiloride-insensitive I SC in FDLE via lavendustin-A sensitive tyrosine kinase and that insulin's action on the amiloride-sensitive I SC of FDLE is mediated through a lavendustin-A insensitive (and presumably tyrosine kinase-independent) pathway.