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

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Abstract
1 The effects of noradenaline (via α1-adrenoceptors) and of the peptidic hormones vasopressin and angiotensin on the Na-K pump have been studied in rat isolated liver cells. 2 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. 3 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. 4 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. 5 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. 6 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. 7 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.