FURTHER-STUDIES ON ALPHA(2)-ADRENOCEPTOR SUBTYPES INVOLVED IN THE MODULATION OF [H-3] NORADRENALINE AND [H-3] 5-HYDROXYTRYPTAMINE RELEASE FROM RAT-BRAIN CORTEX SYNAPTOSOMES

Three selective alpha2A- or alpha2B-adrenergic antagonists (BRL-44408, BRL-41992 and imiloxan) were used in the present study designed to classify the presynaptic alpha2-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 [H-3]noradrenaline and [H-3]5-hydroxytryptamine (5-HT) release from superfused synaptosomes was BRL-44408 greater-than-or-equal-to BRL-41992>>imiloxan. The same rank order was found for the affinities of these compounds for [H-3]yohimbine binding in human platelet membranes, containing only alpha2A-adrenoceptors, but does not correlate with the known affinities for alpha2B-adrenoceptors (BRL-41992 greater-than-or-equal-to imiloxan>BRL-44408). These data support the conclusion that presynaptic alpha2-auto- and heteroreceptors in rat brain cortex do not belong to the alpha2B-subtype and suggest that the modulation of noradrenaline and 5-HT release may be mediated by the alpha2A-subtype.