Lack of a precursor-product relationship between histamine and its metabolites in brain after histidine loading.
Lack of a precursor-product relationship between histamine and its metabolites in brain after histidine loading.
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组氨酸负载后大脑中组胺及其代谢物之间缺乏前体-产物关系。
DOI：
10.1046/j.1471-4159.1996.67051938.x
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发表时间：
1996
影响因子：
4.7
通讯作者：
Green,JP
中科院分区：
文献类型：
--
作者：
Prell,GD;Hough,LB;Khandelwal,J;Green,JP
在腹腔内给予组胺前体l-组氨酸（His）后12 h内，测定大鼠脑中组胺及其主要代谢产物远甲基组胺（t-MH）和远甲基咪唑乙酸（t-MIAA）的水平。与生理盐水给药对照组相比，500 mg/kg剂量给药后1 h组胺的平均水平升高（+ 102%）; t-MH水平未升高。1，000 mg/kg剂量给药后;水平平均组胺水平升高长达7 h，在3 h达到峰值，并在12 h内恢复至对照水平。相比之下，t-MH水平仅在3 h后略有增加;两种剂量后t-MIAA水平保持不变。大多数新形成的组胺不能进行甲基化，这是其在脑中代谢的主要途径，表明组胺可能通过非特异性脱羧后的另一种机制代谢。为了检验这一假设，向其他大鼠注射α-氟甲基组氨酸（α-FIMis; 75 mg/kg，i. p.），一种特异性组氨酸脱羧酶的不可逆抑制剂。在大鼠接受α-FMHis后6小时，与生理盐水处理的对照组相比，平均脑组胺水平降低了30%。在α-FMHis（75 mg/kg）给药后3小时给予His（1，000 mg/kg）并在3小时后检查的大鼠的组胺平均水平高于（+112%）给予α-FMHis的大鼠，随后是生理盐水。t-MH和t-MIAA的水平没有增加。这些结果表明，高剂量的组胺扭曲了大脑中组胺及其甲基化代谢物之间简单的前体产物关系。本文还讨论了组氨酸负载后脑内部分组氨酸发生非特异性脱羧的可能性。这些发现以及His独立于组胺的其他作用，引发了人们对使用His负载作为大脑组胺能功能特异性探针的有效性的质疑。
Levels of histamine and its major metabolites in brain,tele‐methylhistamine (t‐MH) andtele‐methylimidazoleacetic acid (t‐MIAA), were measured in rat brains up to 12 h after intraperitoneal administration ofl‐histidine (His), the precursor of histamine. Compared with saline‐treated controls, mean levels of histamine were elevated at 1 h (+ 102%) after a 500 mg/kg dose; levels of t‐MH did not increase. Following a 1,000 mg/kg dose; levels mean histamine levels were increased for up to 7 h, peaked at 3 h, and returned to control levels within 12 h. In contrast, levels of t‐MH showed a small increase only after 3 h; levels of t‐MIAA remained unchanged after either dose. Failure of most newly formed histamine to undergo methylation, its major route of metabolism in brain, suggested that histamine was metabolized by another mechanism possibly following nonspecific decarboxylation. To test this hypothesis, other rats were injected with α‐fluoromethylhistidine (α‐FMHis; 75 mg/kg, i.p.), an irreversible inhibitor of specific histidine decarboxylase. Six hours after rats received α‐FMHis, the mean brain histamine level was reduced 30% compared with saline‐treated controls. Rats given His (1,000 mg/kg) 3 h after α‐FMHis (75 mg/kg) and examined 3 h later had a higher (+112%) mean level of histamine than rats given α‐FMHis, followed by saline. Levels of t‐MH and t‐MIAA did not increase. These results imply that high doses of His distort the simple precursor‐product relationship between histamine and its methylated metabolites in brain. The possibility that some His may undergo nonspecific decarboxylation in brain after His loading is discussed. These findings, and other actions of His independent of histamine, raise questions about the validity of using His loading as a specific probe of brain histaminergic function.