mitoguazone and 1-methyladenine

Methylglyoxal-bis(guanylhydrazone) diHCl (MGBG), an inhibitor of S-adenosylmethionine decarboxylase, was found to induce starfish oocyte maturation at concentrations above 30 microM. Among several analogs of MGBG three induce oocyte maturation and one lacks the maturation-inducing activity while possessing the S-adenosylmethionine decarboxylase-inhibiting activity. Although MGBG is required during a slightly longer period than the natural hormone 1-methyladenine (1-MeAde), the maturation kinetics are identical. MGBG-induced maturation is sensitive to the same inhibitors as 1-MeAde-induced maturation (theophylline, caffeine, procaine, nicotine, NH4Cl, dansylcadaverine, vinblastine, R24571, and trifluoperazine). Inhibition is reversed by increasing the MGBG concentration. MGBG also induces an increase of protein phosphorylation. MGBG and 1-MeAde were separated on the basis of charcoal adsorption, MgSO4 precipitation, and thin-layer chromatography. MGBG covalently linked to CH-Sepharose 4B induces maturation in oocytes whose jelly layer and vitelline coat have been removed by a moderate pronase treatment, but not in the untreated oocytes. The MGBG-CH-Sepharose 4B beads come in close contact with the plasma membrane only in the pronase-treated oocytes. The mode of action of MGBG and the implications of these results in the purification of the 1-MeAde receptor are discussed.

Topics: Adenine; Adenosylmethionine Decarboxylase; Animals; Female; Guanidines; Meiosis; Mitoguazone; Oocytes; Oogenesis; Phosphoproteins; Polyamines; Solubility; Starfish; Structure-Activity Relationship