Presynaptic α2A/D-autoreceptors in the brain cortex of Cercopithecus aethiops

Abstract

The existence of presynaptic α₂-autoreceptors, and the subtype to which the receptors belong, were studied in the brain cortex from two African green monkeys (Cercopithecus aethiops). Slices of the brain cortex were preincubated with ³H-noradrenaline. The slices were then superfused with medium containing desipramine (1 μM) and stimulated electrically with trains of 72 pulses, 3 Hz. Concentration-response curves of nine α-adrenoceptor antagonists were determined. All antagonists enhanced the stimulation-evoked overflow of tritium, i.e. the release of noradrenaline, indicating the existence of presynaptic α₂-autoreceptors. The EC _30% values of the antagonists (concentrations that increased the evoked overflow of tritium by 30%) were taken as a measure of affinity for the autoreceptors. The subclassification was based on a comparison of these affinity estimates with affinities for α_2A, α_2B, α_2C and α_2D radioligand binding sites and for previously classified α_2A- and α_2D-autoreceptors. The comparison indicates that the α₂-autoreceptors in the brain cortex of Cercopithecus aethiops belong to the genetic α_2A/D and not the α_2B or α_2C subtype. In their pharmacological properties, the autoreceptors are closest to the pharmacological α_2D subtype. The results support the notion that α₂-autoreceptors belong at least predominantly to the α_2A/D subtype of α₂-adrenoceptors.