Mechanism of action of noradrenaline on the sodium-potassium pump in isolated rat liver cells.

Noradrenaline, which mobilizes Ca from intracellular stores, stimulated the Na-K pump in isolated rat liver cells. This resulted in transient decreases in internal Na content and external K concentration. The effect of the hormones was observed in the presence of the beta-adrenergic antagonist propranolol and was blocked by the alpha-antagonist phenoxybenzamine. Prazosin appeared to be 1000 times more potent than yohimbine in suppressing the cell response to the hormone, suggesting that the effect is mediated by an activation of alpha 1-adrenergic receptors. Externally applied ATP and the Ca ionophore A23187 which, in common with alpha-agonists, deplete internal Ca stores in this tissue, similarly stimulated the Na-K pump and transiently decreased internal Na and external K. The effects of noradrenaline and ATP were not additive. Moreover, the cell response to ATP was observed in the presence of the alpha-antagonist phenoxybenzamine, indicating that though acting via separate receptors, noradrenaline and ATP use a common mechanism to alter the carrier. The effect of noradrenaline and A23187 on the Na-K pump was not dependent on the presence of extracellular Ca. In contrast, when the hepatocytes were incubated in Ca-free medium for long periods (cell Ca depletion) the activity of the Na-K pump was increased to a level corresponding to that induced by maximal doses of noradrenaline. In these conditions, noradrenaline and A23187 did not increase the pump activity further. In cells in which the Na content was raised, leading to a 3-fold increase in the Na-K pump activity, noradrenaline continued to be able to stimulate the pump. Again long-term incubations in Ca-free medium increased the pump activity and the effect of noradrenaline was greatly reduced. It is proposed that in isolated rat liver cells alpha-agonists and applied ATP influence the Na-K pump by releasing Ca bound to plasma membranes, thus removing the inhibitory effect of this ion on the Na pump.