H3‐Receptors Control Histamine Release in Human Brain

Abstract

The regulation of histamine release was studied on slices prepared from pieces of human cerebral cortex removed during neurosurgery and labeled with l-[³H]-histidine. Depolarization by increased extracellular K⁺ concentration induced [³H]histamine release, although to a lesser extent than from rat brain slices. Exogenous histamine reduced by up to 60% the K⁺-evoked release, with an EC₅₀ of 3.5 ± 0.5 × 10⁻-⁸M. The H₃-receptor antagonists impromidine and thioperamide reversed the histamine effect in an apparently competitive manner and enhanced the K⁺-evoked release, indicating a participation of endogenous histamine in the release control process. The potencies of histamine and the H₃-receptor antagonists were similar to those of these agents at presynaptic H₃-autoreceptors controlling [³H]histamine release from rat brain slices. It is concluded that H₃-receptors control histamine release in the human brain.