Imidazoleacetic acid, a gamma-aminobutyric acid receptor agonist, can be formed in rat brain by oxidation of histamine.
Imidazoleacetic acid, a gamma-aminobutyric acid receptor agonist, can be formed in rat brain by oxidation of histamine.
复制标题
咪唑乙酸是一种γ-氨基丁酸受体激动剂，可通过组胺的氧化在大鼠脑中形成。
DOI：
10.1046/j.1471-4159.1995.65020818.x
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发表时间：
1995
影响因子：
4.7
通讯作者：
Prell,GD
中科院分区：
文献类型：
--
作者：
Thomas,B;Prell,GD
一般认为，在哺乳动物脑中，组胺仅通过组胺甲基转移酶（HMT）代谢，形成甲基组胺，然后氧化全甲基咪唑乙酸。然而，组胺在外周的氧化代谢产物咪唑乙酸（IAA）也存在于脑和CSF中，并且在HMT抑制后其在脑中的水平增加。为了重新研究大脑是否具有氧化组胺和形成IAA的能力，将[3H]组胺（10 ng）注射到清醒大鼠的侧脑室或枕大池中，并在30 min后断头。在盐水处理大鼠的脑中，回收的大部分放射性是由于远甲基组胺和远甲基咪唑乙酸。然而，一致地回收了显著量的氚化IAA及其代谢物，IAA-核糖核苷酸和IAA-核苷。在大鼠预处理与metoprine，HMT的抑制剂，标记的IAA和它的代谢产物通常包括大部分的组胺的氚代代谢产物。[3 H]脑池内给予组胺仅产生微量的氧化代谢物。IAA是一种强效的GABA-A激动剂，具有多种神经化学和行为效应，由脑中微量的组胺形成，这表明需要重新评估组胺在脑中的代谢途径，并提示组胺与GABA能系统之间相互作用的新机制。
It is generally accepted that in mammalian brain histamine is metabolized solely by histamine methyltransferase (HMT), to formtele‐methylhistamine, then oxidized totele‐methylimidazoleacetic acid. However, histamine's oxidative metabolite in the periphery, imidazoleacetic acid (IAA), is also present in brain and CSF, and its levels in brain increase after inhibition of HMT. To reinvestigate if brain has the capacity to oxidize histamine and form IAA, conscious rats were injected with [3H]histamine (10 ng), either into the lateral ventricles or cisterna magna, and decapitated 30 min later. In brains of saline‐treated rats, most radioactivity recovered was due totele‐methylhistamine andtele‐methylimidazoleacetic acid. However, significant amounts of tritiated IAA and its metabolites, IAA‐ribotide and IAA‐riboside, were consistently recovered. In rats pretreated with metoprine, an inhibitor of HMT, labeled IAA and its metabolites usually comprised the majority of histamine's tritiated metabolites. [3H]Histamine given intracisternally produced only trace amounts of oxidative metabolites. Formation of IAA, a potent GABA‐A agonist with numerous neurochemical and behavioral effects, from minute quantities of histamine in brain indicates a need for reevaluation of histamine's metabolic pathway or pathways in brain and suggests a novel mechanism for interactions between histamine and the GABAergic system.