Effects of noradrenaline, vasopressin and angiotensin on the Na-K pump in rat isolated liver cells

Abstract

The effects of noradenaline (via alpha 1-adrenoceptors) and of the peptidic hormones vasopressin and angiotensin on the Na-K pump have been studied in rat isolated liver cells. The three hormones increased the cytosolic Ca concentration, stimulated the Na-K pump and decreased the internal Na concentration of the cells. The effects were dose-dependent and were blocked by the corresponding antagonists. The simultaneous addition of maximal doses of noradrenaline and angiotensin or vasopressin were not additive suggesting that the hormones use a common mechanism to stimulate the carrier. Incubating the cells in Ca-free medium for long periods (Ca-depletion) increased the Na-K pump activity and reduced the stimulatory action of vasopressin, angiotensin and noradrenaline. The effect of the Ca indicator quin2, used as an intracellular Ca chelator, was also studied. The cells were loaded with a maximal concentration of [3H]-quin2 acetoxymethyl ester in the presence of external Ca for 6 min. The final cell content was 3.1 nmol quin2 mg-1 cell dry wt. In these cells the cytosolic Ca, as monitored from the fluorescence emission of the indicator, was about 200 nM and Na-K pump activity was normal and the cells remained responsive to the three hormones. Loading the cells with quin2 in the absence of external Ca reduced the [Ca]i from 200 nM to about 40 nM and increased the Na-K pump activity but not as a result of a rise in internal Na concentration. In addition, the rat hepatocytes were no longer sensitive to the hormones. It is proposed that Ca inhibits the Na-K pump by binding the internal sites and that vasopressin, angiotensin and noradrenaline stimulate the carrier by interfering with the inhibitory Ca sites.