Biomedical subjects
Publications and source records attributed to J D Milner.
Unilateral nigrostriatal lesions in rats that almost totally depleted striatal dopamine had no effect on striatal levels of dopamine's precursor, tyrosine, nor on those of leucine. Since prolonged electrical stimulation of the slices markedly depletes them of tyrosine (1,2) we conclude that tyrosine can be mobilized from non-dopaminergic striatal cells to augment dopamine release.
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We examined the effect of phenylalanine (50-400 microM) on the electrically stimulated release of endogenous 3,4-dihydroxyphenylethylamine (dopamine or DA) from superfused rat striatal slices. In the absence of tyrosine, phenylalanine (25 microM) partially sustained DA release, but less well than an equimolar concentration of tyrosine. In the presence of tyrosine (50 microM), phenylalanine (in concentrations of greater than or equal to 200 microM) inhibited DA release into the superfusate. This inhibition was not associated with changes in tissue levels of tyrosine or DA, nor was it mimicked by addition of high concentrations of tyrosine or leucine to the medium. We conclude that phenylalanine is a less effective precursor of DA in rat striatum than tyrosine and that it can also act to inhibit DA synthesis, depending on its concentration.
Direct evidence that precursor levels can affect catecholamine release from brain cells has not previously been presented. We observe a dose-dependent relationship between the tyrosine (Tyr) concentration of the superfusing medium and the amount of dopamine (DA) released from rat striatum by trains of electrical pulses. In the absence of exogenous tyrosine, tissue Tyr and DA levels are reduced following stimulation. These findings suggest that DA release from striatal neurons may not be sustained if fluctuations occur in the supply of Tyr to the brain.
1 Excitatory junction potentials (e. j. ps) were recorded with intracellular electrodes from smooth muscle cells of the mouse vas deferens. 2 The dependence of the e.j.p. amplitude on the extracellular calcium ion concentration was determined in the absence or presence of normorphine (50 nM-1 microM) or magnesium (1.2-4.8 mM). 3 The interaction between normorphine and calcium was non-competitive beyond a dose-ratio of 1.5, whereas the interaction between magnesium and calcium was competitive up to the highest dose-ratio investigated (1.9). 4 It is suggested that inhibition by normorphine occurs at least partly by a mechanism different from that of magnesium.