In vitro studies on the uptake of 14C-labelled decamethonium and hexamethonium in mouse liver.

Abstract

The uptake process of 14C‐decamethonium in liver was studied by measuring its uptake in slices incubated in Krebs‐Ringer bicarbonate medium (37°, pH 7.4) and for comparison the 14C‐hexamethonium uptake was measured. At 2 μM the slice‐to‐medium (S/M) ratio for decamethonium was about 3 after 1 hour and continued to increase. The hexamethonium uptake after 1 hour was only 1/3 of the decamethonium uptake. Slices from female and immature male mice accumulated decamethonium to the same extent as slices from male mice, whereas rat liver slices were unable to concentrate decamethonium. In an atmosphere of nitrogen and in the presence of 1 μM 2,4‐dinitrophenol, iodoacetic acid or cyanide the decamethonium uptake was significantly reduced. With increasing concentration of decamethonium the 1‐hour S/M ratio decreased towards a constant value (1.5). Thus the uptake could be divided into a passive and a saturable process. The latter had a maximum capacity of 81 μM kg‐1, h‐1 and a half saturation concentration of 54 μM. With 2 μM the decamethonium S/M ratio was reduced to about 50 % in the presence of 50 μM d‐tubocurarine. The inhibitory effect of 22 μM d‐tubocurarine decreased with increasing decamethonium concentration in accordance with competitive antagonism.