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Further Studies on the Nature of Postsynaptic Dopamine Uptake and Metabolism in Rat Striatum: Sodium Dependency and Investigation of a Possible Role for Carrier‐Mediated Uptake into Serotonin Neurons
Author(s) -
Schoepp Darryle D.,
Azzaro Albert J.
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb07164.x
Subject(s) - nomifensine , homovanillic acid , dopamine , 3,4 dihydroxyphenylacetic acid , chemistry , striatum , endocrinology , postsynaptic potential , medicine , reuptake , serotonin , sodium , dopaminergic , biochemistry , biology , receptor , organic chemistry
The nature of postsynaptic sites involved in the uptake and metabolism of striatal 3,4‐dihydroxyphenylethylamine (dopamine, DA) was investigated. The accumulation of [ 3 H]DA (10 −7 M ) into slices of rat striatum was found to be greatly dependent (>99%) on the presence of sodium ion in the incubation medium. However, the formation of the [ 3 H]dihydroxyphenylacetic acid (DOPAC) and [ 3 H]homovanillic acid (HVA) was only partially reduced in the absence of sodium (DOPAC, 27% of control; HVA, 47% of control). Inhibition of carrier‐mediated DA neuronal uptake with nomifensine (10 −5 M ) significantly decreased DA accumulation (18% of control) and [ 3 H]DOPAC formation (62% of control), but enhanced [ 3 HVA production (143% of control), Inhibition of the 5‐hydroxytryptamine (5‐HT, serotonin) neuronal uptake system with fluoxetine (10 −6 M ) or selective 5‐HT neuronal lesions with 5,7‐dihydroxytryptamine (5,7‐DHT) had no effect on [ 3 H]DOPAC or [ 3 H]HVA formed from [ 3 H]DA in the presence or absence of nomifensine. These results demonstrate that the uptake and subsequent metabolism of striatal DA to DOPAC and HVA is only partially dependent on carrier‐mediated uptake mechanism(s) requiring sodium ion. These data support our previous findings suggesting a significant role for synaptic glial cell deamination and O ‐methylation of striatal DA. Further, experiments with fluoxetine or 5,7‐DHT suggest that 5‐HT neurons do not significantly contribute in the synaptic uptake and metabolism of striatal DA.