title: Dopamine release in human neocortical slices: characterization of inhibitory autoreceptors and of nicotinic acetylcholine receptor-evoked release.
abstract: The autoinhibitory control of electrically evoked release of [3H]-dopamine and the properties of that induced by nicotinic receptor (nAChR) stimulation were studied in slices of the human neocortex. In both models [3H]-dopamine release was action potential-induced and exocytotic. The selective dopamine D2 receptor agonist (-)-quinpirole reduced electrically evoked release of [3H]-dopamine, yielding IC50 and I(max) values of 23 nM and 76%, respectively. Also, the effects of several other subtype-selective dopamine receptor ligands confirmed that the terminal dopamine autoreceptor belongs to the D2 subtype. The autoinhibitory feedback control was slightly operative under stimulation conditions of 90 pulses and 3 Hz, with a biophase concentration of endogenous dopamine of 3.6 nM, and was enhanced under blockade of dopamine reuptake. [3H]-dopamine release evoked in an identical manner in mouse neocortical slices was not inhibited by (-)-quinpirole, suggesting the absence of dopamine autoreceptors in this tissue and underlining an important species difference. Also, nAChR stimulation-induced release of [3H]-dopamine revealed a species difference: [3H]-dopamine release was evoked in human, but not in rat neocortical slices. The nAChRs inducing [3H]-dopamine release most probably belong to the alpha3/beta2subtype, according to the potencies and efficacies of subtype-selective nAChR ligands. Part of these receptors may be located on glutamatergic neurons.
authors.affiliation: Sektion Klinische Neuropharmakologie der Neurochirurgischen Universitätsklinik, Breisacherstrasse 64, D-79106 Freiburg, Germany.
authors.forename: Marlene
authors.initials: M
authors.lastname: Löffler
authors.forename: Berenice
authors.initials: B
authors.lastname: Bubl
authors.forename: Frank
authors.initials: F
authors.lastname: Huethe
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hubbe
authors.forename: J Micheal
authors.initials: JM
authors.lastname: McIntosh
authors.forename: Rolf
authors.initials: R
authors.lastname: Jackisch
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Feuerstein
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000470:Alkaloids / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D017660:Autoreceptors / Q000502:physiology*; D001392:Azocines / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005246:Feedback / Q000187:drug effects; D005260:Female; D016666:Fluvoxamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008875:Middle Aged; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium / Q000378:metabolism; D000093843:Quinolizidine Alkaloids
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000470:Alkaloids; D017660:Autoreceptors; D001392:Azocines; D002118:Calcium; D004294:Domperidone; D004298:Dopamine; D018492:Dopamine Antagonists; D016666:Fluvoxamine; D007555:Isoxazoles; D008376:Maprotiline; D009538:Nicotine; D018733:Nicotinic Antagonists; D011188:Potassium; D011759:Pyrrolidines; D011807:Quinolizines; D011978:Receptors, Nicotinic; D013469:Sulpiride; D014316:Tritium; C088383:3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole; C090025:1,2,3,6-tetrahydro-4-phenyl-1-((3-phenyl-3-cyclohexen-1-yl)methyl)pyridine; C027299:hydroxymaprotilin; C004712:cytisine; D000093843:Quinolizidine Alkaloids