Further studies on α2-adrenoceptor subtypes involved in the modulation of [3H]noradrenaline and [3H]5-hydroxytryptamine release from rat brain cortex synaptosomes

Three selective α(2A)- or α(2B)-adrenergic antagonists (BRL-44408, BRL-41992 and imiloxan) were used in the present study designed to classify the presynaptic α₂-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 ≥ 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 α(2A)-adrenoceptors, but does not correlate with the known affinities for α(2B)-adrenoceptors (BRL-41992 ≥ imiloxan > BRL-44408). These data support the conclusion that presynaptic α₂-auto- and heteroreceptors in rat brain cortex do not belong to the α(2B)-subtype and suggest that the modulation of noradrenaline and 5-HT release may be mediated by the α(2A)-subtype.