Alpha 2-adrenoceptors in rat hypothalamus and cerebral cortex: functional evidence for pharmacologically distinct subpopulations.

The presynaptic alpha 2-adrenoceptors regulating, respectively, [3H]noradrenaline and [3H]5-hydroxytryptamine release were compared in experiments with noradrenaline and clonidine as agonists and the two enantiomers of mianserin as antagonists in rat hypothalamic and cortical synaptosomes depolarized with 15 mM KCl. The affinity of clonidine was 10 times higher at the alpha 2-autoreceptors than at the alpha 2-heteroreceptors. (-)Mianserin antagonized noradrenaline at the heteroreceptors but not at the autoreceptors. In contrast, (+)mianserin did not discriminate between the two receptors. The results support the existence in the rat brain of subtypes of alpha 2-adrenoceptors having different neuronal location, function and pharmacological properties.