Effect of alpha-methyldopa on dopamine synthesis and release in rat striatum in vitro.
The effect of alpha-methyldopa and alpha-methyldopamine (alpha-MDA) on the rate of hydroxylation of radioactive tyrosine was studied in striatal slices from rat brain. This was done by measuring the formation of 3-H-H2O as well as the accumulation of 3-H-dopamine (3-H-DA) from L-3, 5-3-H-tyrosine. alpha-Methyldopa, at tissue concentrations similar to those found in vivo after systemic administration, produced a decrease in both 3-H-H2O and 3-H-DA. The marked decrease (91thyldopa injection, also inhibited 3-H-H2O formation. The inhibitory effect of alpha-methyldopa on 3-H-H2O formation was not reduced by the addition of brocresine, which prevents the formation of alpha-MDA. The effects of alpha-methyldopa and alpha-MDA on the release of 3-H-DA that had been taken up into brain slices, was also studied. Although alpha-methyldopa, 1000 muM, did not increase the release of 3H-DA from tissue, alpha-MDA did. However, the latter was more potent in inhibiting 3-H-H2O formation from 3-H-tyrosine than in releasing 3-H-DA. These results, as well as the close similarity between the percent reduction of 3-H-H2O formation and tissue 3-H-DA levels, suggest that alpha-methyldopa decreases tissue levels of dopamine by inhibiting tyrosine hydroxylase activity in DA neurons.
D000818:Animals; D001834:Body Water / Q000378:metabolism; D001958:Brocresine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003846:Deoxyepinephrine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008750:Methyldopa / Q000494:pharmacology*; D051381:Rats; D014316:Tritium; D014443:Tyrosine / Q000302:isolation & purification / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014316:Tritium; D001958:Brocresine; D014443:Tyrosine; D008750:Methyldopa; D014446:Tyrosine 3-Monooxygenase; D003846:Deoxyepinephrine; D004298:Dopamine