Aldosterone and insulin stimulate amiloride-sensitive sodium transport in A6 cells by additive mechanisms

The individual effects of aldosterone and insulin on amiloride-sensitive Na+ transport in model renal epithelia have been well characterized. However, in the physiological state, many hormones are present concurrently and their interactions need to be addressed. We have found that, over 5 h, the effects of insulin and aldosterone are additive. This indicates that the biochemical pathways are largely independent. To delineate the signaling pathways, we examined the requirement for tyrosine kinases by using genistein, a tyrosine kinase inhibitor. Genistein blocks basal (constitutive) Na+ transport and inhibits insulin- and aldosterone-stimulated Na+ transport. From these results, we conclude that a tyrosine phosphorylation is an important component of amiloride-sensitive Na+ transport.