The effects of L-dopa on the activity of methionine adenosyltransferase: relevance to L-dopa therapy and tolerance.
L-dopa, the major treatment for Parkinson's disease (PD), depletes S-adenosyl-L-methionine (SAM). Since SAM causes PD-like symptoms in rodents, the decreased efficacy of chronic L-dopa administered to PD patients may result from a rebound increase in SAM via methionine adenosyl transferase (MAT), which produces SAM from methionine and ATP. This was tested by administering intraperitoneally saline, or L-dopa to mice and assaying for brain MAT activity. As compared to controls, L-dopa (100 mg/kg) treatments of 1 and 2 times per day for 4 days did not significantly increase MAT activity. However, treatments of 3 times per day for 4 and 8 days did significantly increase the activity of MAT by 21.38% and 28.37%, respectively. These results show that short interval, chronic L-dopa treatments significantly increases MAT activity, which increases the production of SAM. SAM may physiologically antagonize the effects of L-dopa and biochemically decrease the concentrations of L-dopa and dopamine. Thus, an increase in MAT may be related to the decreased efficacy of chronic L-dopa therapy in PD.
Benson
R
R
Meharry Medical College, Department of Physiology, Nashville, TN 37208.
Crowell
B
B
Hill
B
B
Doonquah
K
K
Charlton
C
C
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008715:Methionine / Q000378:metabolism; D008716:Methionine Adenosyltransferase / Q000378:metabolism*; D051379:Mice; D010300:Parkinson Disease / Q000188:drug therapy* / Q000201:enzymology; D012436:S-Adenosylmethionine / Q000378:metabolism
D007980:Levodopa; D012436:S-Adenosylmethionine; D000255:Adenosine Triphosphate; D008715:Methionine; D008716:Methionine Adenosyltransferase