title: Further studies on alpha 2-adrenoceptor subtypes involved in the modulation of [3H]noradrenaline and [3H]5-hydroxytryptamine release from rat brain cortex synaptosomes.
abstract: Three selective alpha 2A- or alpha 2B-adrenergic antagonists (BRL-44408, BRL-41992 and imiloxan) were used in the present study designed to classify the presynaptic alpha 2-auto- and heteroreceptors in the rat brain cortex. The rank order of potency in antagonizing the inhibitory effect of (-)-noradrenaline or clonidine on the K(+)-induced [3H]noradrenaline and [3H]5-hydroxytryptamine (5-HT) release from superfused synaptosomes was BRL-44408 > or = BRL-41992 >> imiloxan. The same rank order was found for the affinities of these compounds for [3H]yohimbine binding in human platelet membranes, containing only alpha 2A-adrenoceptors, but does not correlate with the known affinities for alpha 2B-adrenoceptors (BRL-41992 > or = imiloxan > BRL-44408). These data support the conclusion that presynaptic alpha 2-auto- and heteroreceptors in rat brain cortex do not belong to the alpha 2B-subtype and suggest that the modulation of noradrenaline and 5-HT release may be mediated by the alpha 2A-subtype.
authors.affiliation: Istituto di Richerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gobbi
authors.forename: E
authors.initials: E
authors.lastname: Frittoli
authors.forename: T
authors.initials: T
authors.lastname: Mennini
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003984:Dibenzazepines / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000317:Adrenergic alpha-Antagonists; D003984:Dibenzazepines; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D011942:Receptors, Adrenergic, alpha; C072126:BRL 41992; D012701:Serotonin; D009638:Norepinephrine; C072125:BRL 44408; C044484:Imiloxan