Abstract

Slides of cerebral cortex, cereheilar cortex and gray matter of time spinal cord of rats concentrated carhachol wimicim had been labeled with tritium, and the uptake was largely inhibited by d-tubocurarine and by strychnine. White matter showed little accumulation. Carbachol up to 0.8 M produced no detectable loss of potassium in slices of cerebral cortex, and at low doses the carbachol became concentrated until the ratio between tissue and saline approached that of Potassium. In the absence of glucose there was a fall in potassium content and a low uptake of carhachol, and with high external potassium the tissues were unable to concentrate either potassium or carbachol. With increased concentrations of carbachol time accumulation of the drug showed saturation, and the movements of carbachol were consistent with a monovalent carrier mechanism having a half-saturation constant of 41 µM and a capacity of 156 x 10-9 mol/g/hr. The saturable and curare-sensitive components of entry were similar, and the saturable entry of carhachol was inhibited by d-tubocurarine with an inhibitory constant of 3 µM. The effect of d-tubocurarine in slowing the influx of labeled carbachol could he described by time same procedures as those used in time case of pharmacologic antagonism, and the dose-effect curve and Gaddum's equation for equinctive doses were found to apply to the inward movements of carbachol.