Abstract
The possibility of negative feedback controls of dopamine (DA) synthesis in the dopaminergic terminals of the rat striatum has been investigated by increasing endogenous DA levels. Monoamine oxidase inhibition by pargyline induced a multiphasic change in DA levels. From the initial effect of the monoamine oxidase inhibitor, it was estimated that newly synthesized DA half-life is about 15 minutes and that its synthesis rate is about 27 µg/g/hr. The slower rate of DA increase observed when DA had reached 145% of control levels has been attributed to a reduction of its synthesis. This hypothesis was confirmed by estimating: 1) in vivo, the accumulation of 3H-DA and 3H-methoxydopamine newly synthesized from 3H-tyrosine at different times after either acute or chronic pargyline treatments; 2) in vitro, the 3H-H2O formed during the L-3 ,5-3H-tyrosine-3H-dihydroxyphenylalanine conversion in striatal slices of rats pretreated with pargyline or pheniprazine or preincubated in presence of high concentrations of DA. The effect of DA (10-5 M) on 3H-H2O formation partially was prevented by benztropine (10-6 M). Both changes in 3H-DA accumulation and 3H-H2O formation do not seem to be related to changes in tyrosine specific activity since neither tyrosine levels nor 3H-tyrosine uptake were reduced in our experimental conditions. These data suggest that regulation of DA synthesis is mediated by end product inhibition occurring at the first and rate limiting step of the DA synthesis.
Footnotes
- Received December 15, 1971.
- Accepted April 29, 1972.
- © 1972 by The Williams & Wilkins Co.
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