Manganese administration induces the increased production of dopamine sulfate and depletion of dopamine in Sprague-Dawley rats.
Sprague-Dawley rats were used as an experimental model for investigating the effects of manganese poisoning on the serum levels of unsulfated and sulfated forms of dopamine and its biosynthetic precursors, L-Dopa and L-p-tyrosine. Groups of rats were treated daily with Mn(2+) (20 mg or 40 mg; in the form of MnSO(4)) or Na(+) (20 mg; in the form of Na(2)SO(4)). High performance liquid chromatography (HPLC) analysis of the serum samples taken after a 50-day experimental period revealed that the serum level of dopamine sulfate increased by more than 10 times compared with untreated control rats or rats treated with sodium sulfate. In contrast, there was a dramatic decrease (by as much as 4.8 times) in the serum level of unsulfated dopamine in manganese-treated rats. The serum levels of L-Dopa sulfate and L-p-tyrosine sulfate were also markedly elevated, although not as much as those of dopamine sulfate. Meanwhile, the serum levels of unsulfated L-Dopa and L-p-tyrosine showed no dramatic changes. Atomic absorption spectrophotometric analysis revealed in general an accumulation of manganese in the four organ samples taken from manganese-treated rats. Compared with liver, heart, and kidney, the highest degree of manganese accumulation in manganese-treated rats appeared to be in brain. These results together suggested a role for manganese in stimulating the dopamine-sulfating sulfotransferases in brain, thereby leading to the depletion of dopamine in vivo.
Ranasinghe
J G
JG
Department of Biochemistry and Applied Biosciences, Miyazaki University, Miyazaki 889-21, Japan. liu@uthct.edu
Liu
M C
MC
Sakakibara
Y
Y
Suiko
M
M
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000097:blood*; D006321:Heart / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D007980:Levodopa / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000008:administration & dosage*; D020149:Manganese Poisoning; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000097:blood
D014443:Tyrosine; D008345:Manganese; D007980:Levodopa; D004298:Dopamine