Studies on gossypol, a spermatocidal, anti-viral and anti-parasitic agent

点击翻译按钮获取中文摘要

We have investigated the mechanism of action of gossypol. The spermatocidal activity of gossypol was examined on sperms from surf clam, Spisula solidissima. Our initial attempt was to isolate gossypol binding protein in Spisula sperm membrane. After treating sperm suspension with Triton X-100 containing buffer solution, solubilized gossypol-binding protein fraction was obtained by passing the soluble solution to affinity column. We prepared gossypol-and gossypolone-affinity resins for this purpose. SDS-PAGE analysis showed that there were at least three distinct protein bands stained by Coomassie staining. Further purification of these proteins is in progress.Structural analogs and chemical derivatives of gossypol were examined for their spermatocidal activity, oxygen consumption, and ability of fertilizing oocytes. The results revealed that aldehyde moiety is critical for all gossypol activities. The formation of quinonoid structure is crucial for the formation of gossypolone, which is the active intermediate.The relation between gossypol action and other drugs which block sperm motility, such as calcium channel blockers and tricyclic antidepressants, were also examined.Recently, GABA, an inhibitory neurotransmitter in brain, and its synthesizing enzyme, glutamate decarboxylase, were found in reproductive system. The involvement of GABA and glutamate decarboxylase in reproductive process has been suggested, however, nothing is known. We have found that anti-glutamate decarboxylase antibody recognizes gossypol-binding protein bands of spisula sperm. The study is carrying out to reveal the role of gossypol-binding proteins in fertilization.