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

Abstract

The nature of postsynaptic sites involved in the uptake and metabolism of striatal 3, 4-dihydroxyphenylethylamine (dopamine, DA) was investigated. The accumulation of [3H] DA (10-7 M) into slices of rat striatum was greatly dependent (> 99%) on the presence of NA+ in the incubation medium. The formation of the [3H] dihydroxyphenlacetic acid (DOPAC) and [3H] homovanillic acid (HVA) was only partially reduced in the absence of Na (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 [3H] DOPAC formation (62% of control), but enhanced [3H] 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 [3H] DOPAC or [3H] HVA formed from [3H] DA in the presence or absence of nomifensine. The uptake and subsequent metabolism of striatal DA to DOPAC and HVA is only partially dependent on carrier-mediated uptake mechanisms(s) requiring Na+. Synaptic glial cell deamination and O-methylation of striatal DA have significant roles. 5-HT neurons do not significantly contribute in the synaptic uptake and metabolism of striatal DA.