MANGANESE POISONING--NEW INSIGHTS

Manganese poisoning is discussed as being a clinical model in the study of extrapyramidal disorders. Various technical developments are mentioned which have extended our capabilities for investigating the metabolism of Mn. Some observations are presented on the normal physiology of this element and on some distortions thereof. The high concentration of Mn in malanin granules was noted. These bodies were proposed as possibly reflecting chemical and physical changes underlying some extrapyramidal diseases including Mn poisoning. (auth

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, chlorpromazine (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 (10-3M) 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 physiological and pharmacological compounds control or alter pigmentation