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

1992; Elsevier BV; Volume: 187; Issue: 2 Linguagem: Inglês

10.1016/0006-291x(92)91267-t

1090-2104

Nobuko Hagiwara, H. Tohda, Yasuo Doi, Hugh OʼBrodovich, Yoshinori Marunaka,

Ion Transport and Channel Regulation

We studied the effect of insulin and lavendustin-A (a tyrosine kinase inhibitor) on the short-circuit current (ISC) of primary cultures of fetal distal rat lung epithelium (FDLE). Insulin (2μM) on the basolateral side of the monolayer increased ISC from 5.76±0.83μA/cm2 (SEM, n=7) to 7.23±1.00μA/cm2 (p<0.01) under control conditions, and from 1.00±0.31μA/cm2 to 1.53±0.34μA/cm2 (p<0.05, n=4) when amiloride (10μM) was present on the apical side of the monolayer. Thus insulin increased both the amiloride-sensitive and insensitive ISC with the insulin-induced increase in ISC in the absence of amiloride (1.47±0.22μA/cm2, n=7) being significantly larger than that in the presence of 10μM amiloride (0.53±0.14μA/cm2, n=4; p<0.025). Insulin's effect reached steady state in 1 hr. Lavendustin-A (10 μM), a tyrosine kinase inhibitor, applied to the apical side of the monolayer attenuated but did not completely block insulin's ability to increase in ISC; i.e., insulin increased ISC in lavendustin-A treated monolayers (0.63±0.09μA/cm2, n=5; p<0.0025) but the increase was significantly smaller than that without the pretreatment of lavendustin-A (p<0.05). In the presence of amiloride (10 μM) and lavendustin-A (10 μM) insulin was no longer able to increase ISC (change in ISC = 0.04±0.03μA/cm2, n=6), suggesting that lavendustin-A had blocked the insulin's effect on the amiloride-insensitive ISC. Lavendustin-A (10 μM) had no significant effect on the basal ISC in control and amiloride treated monolayers. Our studies demonstrate that insulin increases amiloride-insensitive ISC in FDLE via lavendustin-A sensitive tyrosine kinase and that insulin's action on the amiloride-sensitive ISC of FDLE is mediated through a lavendustin-A insensitive (and presumably tyrosine kinase-independent) pathway.