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

Abstract

SUMMARY1. 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.2. The effect of the hormones was observed in the presence of the f8-adrenergic antagonist propranolol and was blocked by the a-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 ac-adrenergic receptors.3. Externally applied ATP and the Ca ionophore A23187 which, in common with a-agonists, deplete internal Ca stores in this tissue, similarly stimulated the Na-K pump and transiently decreased internal Na and external K. 4. The effects of noradrenaline and ATP were not additive. Moreover, the cell response to ATP was observed in the presence ofthe a-antagonist phenoxybenzamine, indicating that though acting via separate receptors, noradrenaline and ATP use a common mechanism to alter the carrier.5. 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.6. 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.7. It is proposed that in isolated rat liver cells ac-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.

Effects of apamin on α‐adrenoceptor‐mediated changes in plasma potassium in guinea‐pigs

“…It therefore seems possible that the amidephrine-induced hypokalaemia is at least in part due to an a1-adrenoceptor induced K+-uptake, perhaps by the liver. Recent work with isolated liver cells of the rat has shown that oxl-adrenoceptor agonists, and other agents which elevate cytosolic Ca2+, increase the Na+/K+-pump rate which results in a net uptake of K+ (Capiod, Berthon, Poggioli, Burgess & Claret, 1982;Berthon, Burgess, Capiod, Claret & Poggioli, 1983). The time course and magnitude of this effect are comparable to the hypokalaemia found in vivo (see Figure 2) being maximal at 30s and returning to baseline within 3 to 5 min.…”

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

“…The present results are the first indication that, in common with noradrenaline (Burgess et al, 1981;Capiod et al, 1982Berthon et al, 1983, angiotensin and vasopressin rapidly stimulate the Na-K pump in rat isolated liver cells. The action ofeach hormone was dose-dependent, blocked by preincubation with the corresponding antagonist and occured via activation of different types of receptors (see also Campanile et al, 1982;Keppens et al, 1982;Jard, 1983).…”

“…In rat isolated liver cells, it has been shown that Rb behaves in a very similar way to K ions and can be used as a convenient substitue for K ions (Weiss & Putney, 1978;Ihlenfedt, 1981;Fehlmann & Freychet, 1981;Berthon et al, 1983). Routinely, a 1 ml sample (ca.…”

“…Rat hepatocytes were incubated with the hormones and the 86Rb influx marker (86Rb) for 90 s. Table 1 shows that angiotensin (1 nM) and vasopressin (10 nM), as well as noradrenaline (1 pM), significantly increased both the total 86Rb influx and the ouabain-sensitive uptake indicating Na-K pump stimulation. The lack of effect of the hormones on the ouabain-resistant 86Rb influx ( (Charest et al, 1983;Berthon et al, 1984) does not increase K permeability in rat isolated liver cells (Burgess et al, 1981;Berthon et al, 1983;Jenkinson et al, 1983). ists, 1-sarcosine, 8-isoleucine angiotensin (Sar-Ileangiotensin; 50 nM) and d(CH2)5Tyr(Et)Valineargininevasopressin (cyclo-(tyr)-vasopressin; 50 nM), which by themselves had no effect on the Na-K pump, totally abolished the cell response to their corresponding hormones.…”

“…The second aim was to investigate the role of Ca in the cell response to these three hormones. This was prompted by the previous finding that the stimulatory action of noradrenaline is altered in rat liver cells depleted of their Ca by long incubation periods in low-Ca media (Capiod et al, 1982;Berthon et al, 1983). External Ca was reduced by EGTA and cytosolic Ca either by long incubation periods in low-Ca media or by using the intracellular Ca chelator quin2 .…”