Gossypol Induced Hypokalemia Mechanism

Gossypol is a potential male contraceptive with affirmative effect. However, some of the subjects who took gossypol suffered from hypokalemia. This has become the main obstacle in its use. In the present study, the effects of gossypol acetic acid on Na+ and K+ transmemberane fluxes in human red cells treated with PCMBS (p-chloromercuribenzene sulphonate), and on internal Na+ and K+ concentrations of the fresh human red cells were studied, and intracellular Na+ and K+ concentrations and (Na+,K+) cotransport activities of volunteers taking gossypolhave also been determined. In addition, by means of electron microscope cytoch-emical technique, the effect of gossypol on the Na+-K+-ATPase in the fresh and P CMBS-treated human red cells was observed. The results provide a new possible e vidence for elucidating the mechanism of hypokalemia caused by gossypol.At first, it was found that gossypol slowed down Na+, K+ effluxes from the PCMBS-treated red cells. At 2 umol/L gossypol, Na+ and k+ concentrations in fluxmedia decreased by 14x and 4x respectively, in comparison with control. By further study to compare the effect of gossypol on Na+ and K+ transport with that of ouabain, it was found that ouabain-sensitive Na outward transport rates were 5.28+-0.14 and 5.43+-0.38 mmol/L RBC.h-1 respectively in the absence or presenceof 2 umol/L of gossypol. There is no significant difference between the two g roups CP>0.05). it indicates that gossypol may have no significant inhibitory ef fect on Na+-K+-ATPase. On the other hand, gossypol slowed down the ouabain- resi stant Na+ outward transport rate by 30% (P<0.001). The effect of gossypol was further compared with that of furosemide. Gossypol inhibited furosemide-sen-siti ve Na+, K+ effluxes (Na+,K+ cotransport activity) by 69% and 61% respectively, b ut had no significantly inhibitory effect on furosemide-resistant Na+ and K+ eff luxes. The result suggests that gossypol might be an inhibitor of outward (Na+,K +) cotransport in human red cells.Besides, the relationship between the dose a nd response of gossypol for inhibiting (Na+, K+) cotransport was studied. The in...