No abstract

In order to study cation transport in vivo we have measured the changes in plasma and intra-erythrocytic rubidium concentrations following an oral load of rubidium chloride. The changes in plasma rubidium concentration are related to the distribution of rubidium to all the body tissues and the changes in intra-erythrocytic rubidium concentrations provide an example of rubidium uptake by one particular tissue. In eight healthy volunteers pretreatment with a loading dose of digoxin (20 micrograms/kg) enhanced the rise in plasma rubidium concentrations and attenuated the rise in intra-erythrocytic rubidium concentrations after the oral load of rubidium chloride. Ten patients with chronic renal failure, compared with a well-matched control group, were found to have changes similar to, but more marked than, those caused by digoxin, i.e. a much greater rise in plasma rubidium concentrations and a much smaller rise in intra-erythrocytic rubidium concentrations, after the oral load of rubidium chloride. These findings are consistent with wide-spread reduction in Na+, K+-ATPase activity in subjects who have taken a loading dose of digoxin and patients with chronic renal failure. They are, therefore, consistent with the findings of previous studies in vitro and show that it is possible to demonstrate changes in cation transport in vivo.

The effects of carbamazepine (CBZ) on brain 5-hydroxytryptamine (5-HT) function were investigated in rodents pretreated with CBZ acutely or for 14 days. In behavioural experiments, mice pretreated with 14 days CBZ showed increased 5-HT2-mediated head twitch behaviour after injection of carbidopa (25 mg/kg) followed by 5-hydroxytryptophan (5-HTP, 100 mg/kg). However, no change in head twitches after 5-methoxy,N,N,-dimethyltryptamine (5MeODMT 5.0 mg/kg), a direct agonist, was observed. Chronic CBZ administration to rats did not alter either the behavioural syndrome induced by 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT, 1.0 mg/kg), an index of postsynaptic 5-HT1A responses, or hypothermia after 8-OH-DPAT (0.5 mg/kg) which is thought to reflect presynaptic 5-HT1A activity. Both hyperactivity and the behavioural syndrome seen after tranylcypromine (20 mg/kg) followed by L-tryptophan (100 mg/kg) were decreased by prior treatment with CBZ (14 days). Accumulation of 5-HTP after administration of the amino acid decarboxylase inhibitor NSD1015 (100 mg/kg) was decreased after acute CBZ (50 mg/kg) in hippocampus. However, after 14 days oral treatment no change in this measure of 5-HT synthesis was seen, in either hippocampus or frontal cortex. CBZ (50 microM) added to superfused brain slices did not affect potassium-stimulated [3H]-5-HT release. However, hippocampal slices from rats pretreated with CBZ (14 days) showed increased potassium-stimulated [3H]-5-HT release. CBZ (14 days) did not alter 5-HT2 binding in rat frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to study cation transport in vivo we have measured the changes in plasma and intra-erythrocytic rubidium concentrations after the oral administration of rubidium chloride. In this paper we describe our findings in 22 patients with untreated essential hypertension, compared with the findings in 22 carefully matched control subjects. Our findings in patients receiving short-term digoxin therapy and in patients with chronic renal failure are also included for comparison. Whereas the findings in patients receiving digoxin and in patients with chronic renal failure are compatible with a widespread reduction in sodium, potassium-ATPase activity in vivo, the findings in patients with untreated essential hypertension are not. Further analysis of the data and a similar study of the disposition of 42K after the intravenous administration of 42KCl suggest that in vivo net cation transport is enhanced in the erythrocytes of patients with untreated essential hypertension.

We have studied the effects of digoxin on cation transport in vivo by measuring the changes in plasma and red cell rubidium concentrations following an oral load of rubidium chloride. In eight patients who had been taking digoxin for 7 to 10 days (mean plasma digoxin concentration 1.3 ng ml‐1) the rise in plasma rubidium concentrations was enhanced and the rise in red cell rubidium concentrations was attenuated following the oral load of rubidium chloride, by comparison with the changes in well‐matched controls. In contrast, the disposition of rubidium was not altered in 12 patients who had been taking digoxin for more than 3 months (mean plasma digoxin concentration 1.1 ng ml‐1). These results suggest that the inhibitory effects of digoxin on cation transport are detectable in vivo during short‐term therapy, but not during long‐term therapy, and confirm our previous in vitro findings.