Modulation of Histamine Release and Synthesis in the Brain Mediated by α2‐Adrenoceptors

Abstract

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 α2-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 clo-nidine and oxymetazoline acted as partial agonists, oxymeta-zoline even behaving as an apparent antagonist. In vivo clo-nidine 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 α₂-adrenoceptors presumably located on histaminergic axons control release and synthesis of histamine in the brain.