title: Subclassification of presynaptic alpha 2-adrenoceptors: alpha 2D-autoreceptors in mouse brain.
abstract: The study was devised to classify, by means of antagonist affinities, the presynaptic alpha 2-autoreceptors in mouse cerebral cortex in terms of alpha 2A, alpha 2B, alpha 2C and alpha 2D. A set of antagonists was chosen that was able to discriminate between the four subtypes. Slices of the cortex were preincubated with 3H-noradrenaline and then superfused and stimulated electrically. The stimulation periods used (4 pulses, 100 Hz) did not lead to alpha 2-autoinhibition as shown by the lack of an increase by rauwolscine of the evoked overflow of tritium. The alpha 2-selective agonists 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and alpha-methylnoradrenaline reduced the evoked overflow. All 10 antagonists shifted the concentration-inhibition curve of UK 14,304 to the right. Rauwolscine also shifted the concentration-inhibition curve of alpha-methylnoradrenaline to the right. pKd values of the antagonists were calculated from the shifts. The pKd values of rauwolscine against UK 14,304 and alpha-methylnoradrenaline were very similar (8.0 and 7.9, respectively). Comparison with antagonist affinities for prototypic native alpha 2 binding sites, alpha 2 binding sites in cells transfected with alpha 2 subtype genes, and previously classified presynaptic alpha 2-adrenoceptors--all taken from the literature--indicates that the alpha 2-autoreceptors in mouse brain cortex are alpha 2D. This is the first subtype determination of alpha 2-autoreceptors in the mouse. It supports the hypothesis that at least the majority of alpha 2-autoreceptors belong to the alpha 2A/D branch of the alpha 2-adrenoceptor tree.
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D017660:Autoreceptors / Q000145:classification* / Q000187:drug effects; D001667:Binding, Competitive; D001921:Brain / Q000502:physiology*; D000068438:Brimonidine Tartrate; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017729:Presynaptic Terminals / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification* / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D017660:Autoreceptors; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D013779:Tetrodotoxin; D000068438:Brimonidine Tartrate