Glial cells excessive release

As shown in Fig. 3 (Top Panel), dietary tyrosine is transported into axon terminals of DA neurons and converted in the cytoplasm to DOPA by the rate limiting enzyme TH. DOPA is then rapidly decarboxylated by DDC to DA which is taken up and stored in synaptic vesicles until release. Excess newly synthesized DA is metabolized by mitochondrial monoamine oxidase (MAO) to DOPAC which rapidly diffuses out of neurons and is taken up and converted to homovanillic acid (HVA) by catechol-O-methyltransferase (COMT)-containing glial cells in the neuropil (Hansson and Sellstrom, 1983 Kimelberg, 1986). Upon arrival of an action potential at the axon terminal, vesicular DA is released into the synapse via calcium-dependent exocytosis where it is free to interact with stimulatory Di and/or inhibitory D2 DA receptors on postsynaptic target cells and inhibitory D2 autoreceptors on presynaptic terminals. A major portion of DA is removed from the synapse by high affinity DA transporters located on presynaptic terminals, and recaptured DA is either metabolized to DOPAC by mitochondrial MAO or stored in synaptic vesicles for subsequent re-release. A small portion of DA can also be taken up from the synapse by glia and metabolized to 3-methoxytyramine (3MT) and HVA. 

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