REGULATION OF TYROSINASE ACTIVITY IN MOUSE MELANOMA AND SKIN BY CHANGES IN MELANOSOMAL MEMBRANE PERMEABILITY.

Compounds which are known to labilize biological membranes have been demonstrated to increase tyrosinase activity in the B-16 melanoma and newborn mouse skin. Detergents, bile acids, chlorpromazin (CPZ), neutral steroids and proteases all increase melanosomal tyrosinase activity. Digitonin (0.5%) produced approximately a five fold increase in tyrosinase activity and released 50% of the enzyme from the melanosome. CPZ (10-5M) produced a 2.7 fold increase in tyrosinase activity without releasing the enzyme from the melanosome. The CPZ-induced activition of tyrosinase was decreased by the membrane stabilizer, chloroquine and abolished by prior treatment of the melanosomes with digitonin. Alteration of the outer melanosomal membrane by digitonin and CPZ was confirmed by electron microscopy. The results suggest that the membrane surrounding the melanosome regulates the accessibility of eh substrate tyrosine to the tyrosinase molecule inside the organelle. A change in membrane permeability may be the mechanism by which certain physio-logical and pharmacological compounds control or alter pigmentation. [ABSTRACT FROM AUTHOR]