RAT AND MOUSE BRAIN HISTAMINE N‐METHYLTRANSFERASE: MODULATION BY METHYLATED INDOLEAMINES 1
RAT AND MOUSE BRAIN HISTAMINE N‐METHYLTRANSFERASE: MODULATION BY METHYLATED INDOLEAMINES 1
复制标题
大鼠和小鼠脑组胺 N-甲基转移酶：甲基化吲哚胺 1 的调节
DOI：
10.1111/j.1471-4159.1978.tb06548.x
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发表时间：
1978
影响因子：
4.7
通讯作者：
W. G. Ohlsson
中科院分区：
文献类型：
--
作者：
O. Z. Sellinger;R. Schatz;W. G. Ohlsson
报道了一种大鼠和小鼠脑组织组胺N-甲基转移酶(HMT，EC 2.1.1.8)的纯化工艺，获得了87倍纯化的大鼠脑和166倍纯化的小鼠脑酶。纯化的HMT(相对分子质量29,000)可被许多生理和药理活性的胺所抑制，其中包括几个甲基化吲哚胺，其浓度高于5±10-6M。当浓度低于1±10-7M时，大多数甲基化吲哚胺刺激HMT，前提是组胺维持在或接近其作为HMT底物的最佳浓度，即1±10-5M。对抑制过程的性质的研究揭示了多巴胺对HMT的非竞争性抑制，而不是大多数甲基化吲哚胺对该酶的竞争抑制。增加组胺浓度超过最佳值，即达到抑制水平，会导致较少的刺激。这些发现支持这样一种观点，即MSO在选定的脑细胞中引起几种甲基化吲哚胺的形成，这些甲基化吲哚胺能够刺激HMT(可能还有其他甲基转移酶，见Salaset al.，1977)，从而导致大脑中S-腺苷-L-蛋氨酸水平的耗竭，先前报道(Schatz&Sellinger，1975b)。
A purification procedure for rat and mouse brain histamine N‐methyltransferase (HMT, EC 2.1.1.8) is described which achieves the preparation of 87‐fold purified rat brain and 166‐fold purified mouse brain enzyme. The purified HMT (MW 29,000) is inhibited by a number of physiologically and pharmacologically active amines, among them several methylated indoleamines, at concentrations above 5 ± 10‐6M. At concentrations below 1 ± 10‐7M, most of the methylated indoleamines stimulate HMT, provided histamine is maintained at, or close to, its optimal concentration as an HMT substrate, namely 1 ± 10‐5M. A study of the nature of the inhibitory process revealed a non‐competitive inhibition of HMT by dopamine as against a competitive inhibition of the enzyme by most methylated indoleamines. Increasing the concentration of histamine beyond the optimal value, i.e. to inhibitory levels, resulted in less stimulation. The findings support the notion that MSO elicits the formation in selected brain cells of supranormal amounts of several methylated indoleamines which are able to stimulate HMT (and possibly other methyltransferases, see Salaset al., 1977), thereby causing the depletion of the cerebral levels of S‐adenosyl‐L‐methionine, reported previously (Schatz & Sellinger, 1975b).