Modulation of histamine release and synthesis in the brain mediated by alpha 2-adrenoceptors.

The adrenergic regulation of histamine release was studied in rat brain slices labeled with L-[3H]histidine. Noradrenaline in increasing concentrations progressively inhibited K+-evoked [3H]histamine release from cortical slices, whereas phenylephrine and isoprenaline were ineffective. Yohimbine, a preferential alpha 2-adrenoceptor antagonist, reversed the noradrenaline effect in an apparently competitive manner and with a mean Ki value of 30 nM. Phentolamine reversed the noradrenaline effect with a similar potency, whereas propranolol was ineffective. The imidazolines clonidine and oxymetazoline acted as partial agonists, oxymetazoline even behaving as an apparent antagonist. In vivo clonidine also inhibited [3H]histamine formation in cerebral cortex, an effect reversed by the administration of yohimbine. However, yohimbine failed to increase significantly [3H]histamine release in vitro and [3H]histamine formation in vivo, suggesting that adrenergic receptors are not activated by endogenous noradrenaline released under basal conditions. It is concluded that adrenergic alpha 2-adrenoceptors presumably located on histaminergic axons control release and synthesis of histamine in the brain.