title: Neurons expressing individual enzymes of dopamine synthesis in the mediobasal hypothalamus of adult rats: functional significance and topographic interrelations.
abstract: Besides dopaminergic (DA-ergic) neurons having all enzymes of DA synthesis, tyrosine hydroxylase (TH) and aromatic l-amino acid decarboxylase (AADC), "monoenzymatic" neurons expressing only one of them were found in the brain, mostly in the mediobasal hypothalamus (MBH). The aim of this study was to test our hypothesis that DA is synthesized by monoenzymatic neurons, i.e. l-3,4-dihydroxyphenylalanine (l-DOPA), which produced in the monoenzymatic TH neurons is transported in the monoenzymatic AADC neurons for DA synthesis. Incubation of MBH in Krebs-Ringer solution with l-leucine, a competitive inhibitor of l-DOPA uptake, was used to prevent a hypothetical l-DOPA capture into AADC-containing neurons. Incubation of the substantia nigra containing DA-ergic neurons under the same conditions served as the control. According to our data, the l-leucine administration provoked a decrease of DA concentration in MBH and in the incubation medium but not in the substantia nigra and respective incubation medium, showing a decrease of cooperative synthesis of DA in MBH. This conclusion was supported by an observation of higher concentration of l-DOPA in the incubation medium under perfusion of MBH with Krebs-Ringer solution containing tolcapone, an inhibitor of catechol-O-methyltransferase, and l-leucine than under perfusion with the same solution, but without l-leucine. Functional interaction between monoenzymatic TH and AADC neurons was indirectly confirmed by finding in electron microscopy their close relations in MBH. Besides monoenzymatic AADC neurons, any AADC-possessing neurons, catecholaminergic and serotoninergic, apparently, could participate in DA synthesis together with monoenzymatic TH neurons. This idea was confirmed by the observation of close topographic relations between monoenzymatic TH neurons and those containing both enzymes, i.e. DA-ergic, noradrenergic or adrenergic. Thus, monoenzymatic neurons possessing TH or AADC and being in close topographic relations can synthesize DA in cooperation.
authors.affiliation: Laboratory of Neural and Neuroendocrine Regulations, Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov St., Moscow 119334, Russia. Electronic address: michael.ugrumov@mail.ru.
authors.forename: M
authors.initials: M
authors.lastname: Ugrumov
authors.affiliation: Laboratoire de Pathophysiologie des maladies du système nervoux central, UMR5 INSERM 952, IFR 83, Université P. et M. Curie, 7 quai St. Bernard, 75252 Paris Cedex 05, France.
authors.forename: J
authors.initials: J
authors.lastname: Taxi
authors.affiliation: Laboratory of Neural and Neuroendocrine Regulations, Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov St., Moscow 119334, Russia.
authors.forename: T
authors.initials: T
authors.lastname: Pronina
authors.affiliation: Laboratory of Neural and Neuroendocrine Regulations, Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov St., Moscow 119334, Russia.
authors.forename: A
authors.initials: A
authors.lastname: Kurina
authors.affiliation: Laboratory of Neural and Neuroendocrine Regulations, Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov St., Moscow 119334, Russia; Laboratoire de Pathophysiologie des maladies du système nervoux central, UMR5 INSERM 952, IFR 83, Université P. et M. Curie, 7 quai St. Bernard, 75252 Paris Cedex 05, France.
authors.forename: A
authors.initials: A
authors.lastname: Sorokin
authors.affiliation: Laboratory of Neural and Neuroendocrine Regulations, Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov St., Moscow 119334, Russia.
authors.forename: A
authors.initials: A
authors.lastname: Sapronova
authors.affiliation: IINS, UMR CNRS 5297, Université Bordeaux Segalen, 146 rue Léo Saignat, 33076 Bordeaux-Cedex, France.
authors.forename: A
authors.initials: A
authors.lastname: Calas
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000008:administration & dosage; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007930:Leucine / Q000008:administration & dosage; D007980:Levodopa / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D046509:Tissue Culture Techniques; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D002491:Central Nervous System Agents; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D007930:Leucine; D004298:Dopamine
keywords: aromatic l-amino acid decarboxylase; dopaminergic neuron; hypothalamus; l-DOPA; rat; tyrosine hydroxylase