Inhibition by gossypol of phospholipid-sensitive Ca2+-dependent protein kinase from pig testis

Biochim Biophys Acta. 1985 May 8;839(3):276-80. doi: 10.1016/0304-4165(85)90009-1.


Gossypol, a polyphenolic binaphthalene-dialdehyde extracted from cotton plants which possesses male antifertility action in mammals, is a potent inhibitor of phospholipid-sensitive Ca2+-dependent protein kinase from pig testis. Gossypol inhibited Ca2+-dependent activity of the enzyme without affecting its basal activity. The IC50 value (concentration causing 50% inhibition) was 31 microM when lysine-rich histone was used as substrate. Kinetic analysis indicated that the compound inhibited the enzyme non-competitively with respect to ATP (Ki = 31 microM) or lysine-rich histone (Ki = 30 microM), and competitively with respect to phosphatidylserine (Ki = 2.1 microM). With Ca2+, irrespective of the presence or absence of 1,3-diolein, the compound lowered Vmax and increased the apparent Ka for Ca2+. The compound also inhibited phosphorylation by the enzyme of high-mobility-group 1 protein (one of the endogenous substrates in the testis for the enzyme located in nucleosome), with an IC50 value of 88 microM. These results suggested that a phospholipid-sensitive Ca2+-dependent protein phosphorylation system in the testis is involved in the regulation of spermatogenesis.

MeSH terms

  • Animals
  • Gossypol / pharmacology*
  • Kinetics
  • Male
  • Phosphorylation
  • Protein Kinase C
  • Protein Kinase Inhibitors*
  • Spermatogenesis / drug effects
  • Swine
  • Testis / enzymology*


  • Protein Kinase Inhibitors
  • Protein Kinase C
  • Gossypol