Relationships between hepatic melanogenesis and respiratory conditions in the newt, Triturus carnifex.

The Kupffer cells (melanomacrophages) in the livers of lower vertebrates contain varying quantities of melanin according to the season. Specimens of Triturus carnifex raised for 2 months at 6 degrees C and then transferred to water at 22 degrees C show a rapid increase in the hepatic accumulation of the pigment. The Kupffer cells make up more than one fourth of the liver mass in chlorbutol-anesthetized animals isolated for 6-7 hr in hypoxic water at 18 degrees C (to bring the oxygen content in a 620-mL respiratory chamber from 1.1 ppm to 0.0). Thus, hepatic melanin is synthesized when the newt's oxygen supply is inadequate to meet its metabolic needs; melanogenesis, however, requires the presence of oxygen and does not occur in anesthetized specimens immersed in a totally anoxic fluid such as paraffin oil. The intraperitoneal injection prior to hypoxic treatment of 1 mg/g of body weight of kojic acid (inhibitor of the enzyme tyrosinase which catalyzes melanin synthesis) blocks melanogenesis and doubles oxygen consumption. The combination of hypoxia and tyrosinase inhibition causes permanent damage to essential functions of the nervous system, while hypoxic treatment alone has no irreversible consequences. The genic expression of tyrosinase in hypoxia appears to be a physiological response aimed at prolonging survival time in anaerobiosis by lowering the metabolic level; melanin would be an inert subproduct of this function.