[Expression of the enzymes of dopamine synthesis in non-dopaminergic neurons: functional significance and regulation].
Dopamine(DA), the most widely distributed in the nervous system and functionally important chemical signal, is synthesized in DA-ergic neurons from L-tyrosine by means of two enzymes, tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). Apart from the enzymes, specific DA transporter is an attribute of DA-ergic neurons. In the mid eighties of the last century, in addition to DA-ergic neurons, those expressing only one enzyme, TH or AADC, have been discovered. These "monoenzymatic" neurons occurred to be more numerous and more widely distributed in the brain compared to DA-ergic neurons that manifests their wide involvement to the brain functioning. It has been demonstrated that the monoenzymatic neurons expressing complementary enzymes of DA synthesis produce this neurotransmitter in cooperation. In this case, L-tyrosine is transformed to L-DOPA in TH containing neurons that is followed by L-DOPA release and uptake from the intercellular space to AADC containing neurons for DA synthesis. Moreover, the L-DOPA uptake to DA-ergic or serotoninergic neurons results either in the increase or the onset of DA synthesis in addition to serotonin, respectively. The expression of the enzymes of DA synthesis in non-dopaminergic neurons is one of the adaptive reactions serving to compensate the functional insufficiency of DA-ergic neurons. For instance, hyperprolactinemia and the deficiency of DA, prolactin-inhibiting hormone, which is developed under degeneration of DA-ergic neurons of the arcuate nucleus, are compensated with time due to the increase of the number of monoenzymatic neurons and cooperative synthesis of DA in the nucleus. It is supposed that the same compensatory cooperative synthesis of DA is turned on under the degeneration of DA-ergic neurons of the nigrostriatal system that is manifested by the appearance of non-dopaminergic neurons expressing enzymes of DA synthesis in the deafferentated striatum. The expression of the enzymes of DA synthesis in non-dopaminergic neurons is under the control by intercellular signals, catecholamines, neurotrophic (growth) factors and, perhaps, hormones. Thus, non-dopaminergic monoenzymatic neurons expressing enzymes of DA synthesis produce this neurotransmitter in cooperation that is a compensatory reaction under functional insufficiency of DA-ergic neurons, in neurodegenerative diseases, hyperprolactinemia and Parkinson's disease, in particular.
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Ugriumov
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000502:physiology*; D001921:Brain / Q000502:physiology; D003342:Corpus Striatum; D004298:Dopamine / Q000096:biosynthesis*; D006801:Humans; D006966:Hyperprolactinemia / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration; D009434:Neural Pathways; D009474:Neurons / Q000201:enzymology*; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra; D009435:Synaptic Transmission; D014446:Tyrosine 3-Monooxygenase / Q000502:physiology*
D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine