Regulation of metallothionein-I+II levels in specific brain areas and liver in the rat: role of catecholamines.

Abstract

The role of the catecholamines noradrenaline, adrenaline and dopamine on metallothionein (MT) levels of specific areas of the rat brain has been studied. MT-I or MT-I + II levels were measured by radioimmunoassay using specific antibodies that cross-react only slightly with human MT-III (growth inhibitory factor, GIF). The inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine (MPT), which depletes brain dopamine, noradrenaline, and adrenaline, increased MT levels in all brain areas studied (frontal cortex, cortex, medulla oblongata plus pons, midbrain, striatum, hippocampus, hypothalamus, and cerebellum) when considering the results of two separate experiments. The alpha- and beta-receptor blockers, phentolamine, and propranolol, alone or together, did not increase brain MT levels in any area of the brain, suggesting that the effect of MPT in vivo is related to inhibition of the synthesis of dopamine rather than of noradrenaline and adrenaline. Dopamine, noradrenaline, and serotonin increased MT-I levels in primary cultures of neurons, whereas decreased them in astrocyte-enriched primary cultures. Since MT-I levels are about ten times higher in astrocytes than in neurons, the increased brain MT levels induced by MPT may reflect the suppression of the normal inhibitory effect of dopamine on astrocyte MT levels. The increase in MT concentrations induced in most parts of the brain by immobilization stress was not prevented by MPT, phentolamine, or propranolol, suggesting that it was not mediated by the central monoamines.