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Gossypol inhibition of adenylate cyclase
Authors:K L Olgiati  D G Toscano  W M Atkins  W A Toscano
Institution:Charles A. Dana Laboratory of Toxicology, Harvard University School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115 USA
Abstract:Gossypol, a polyphenolic binaphthalene -dialdehyde reputed to exert contraceptive action in males, reversibly inhibits adenylate cyclase ATP pyrophosphate lyase (cyclizing), EC 4.6.1.1] in a concentration-dependent manner. In membranes prepared from a variety of organs, the half-maximal inhibitory concentration (IC50) ranges from 75 microM (rat Leydig tumor cells) to 250 microM (rat liver membranes). Kinetic studies using partially purified catalytic subunit isolated from bovine testis show that gossypol is competitive with ATP with an apparent Ki of 110 microM. These data suggest that gossypol inhibition of adenylate cyclase is due to direct interaction at the nucleotide-binding domain of the catalytic subunit of the enzyme.
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