The inhibition of Na+, K+ ATPase by gossypol has been proposed as a mechanism for the hypokalemia occurring in some patients receiving this drug. Gossypol acetic acid, 3 microM (higher concentration than present clinically), did not inhibit this enzyme prepared from erythrocytes from 5 humans. Thus, it is unlikely that gossypol inhibition of the usual form of this enzyme is the mechanism for the initiation of the hypokalemia.
PIP: Whether gossypol inhibits the enzyme Na+,K+ ATPase, in human red blood cell membranes, a theory proposed to account for the low calcium levels seen in people who take gossypol, was tested. In volunteers taking 30 mg racemic gossypol, gossypol levels of 40 ng/ml (-enantiomer) and 100 ng/ml (+ enantiomer) were detected. In this experiment, the initial gossypol acetic acid concentration was 1.8 mcg/ml (3.1 mcM). The ATPase assay of erythrocyte membranes involved an assay for inorganic phosphate released, controlling for the ouabain-sensitive ATPase activity. Gossypol did not inhibit ATPase in erythrocytes from any of 5 volunteers, including 2 subjects of Chinese ancestry and 3 of European stock. Thus it is unlikely that inhibition of ATPase from red blood cells, the usual form of this enzyme, initiates hypokalemia.