Prell G D, Khandelwal J K, Burns R S, Green J P
Department of Pharmacology, Mount Sinai School of Medicine of the City University of New York, New York.
J Neurochem. 1988 Apr;50(4):1194-9. doi: 10.1111/j.1471-4159.1988.tb10592.x.
Similar to metabolites of other aminergic transmitters, histamine metabolites of brain, tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA), could have a concentration gradient between rostral and caudal sites of CSF. To test this hypothesis, cisternal and lumbar CSF samples were collected in pairs from eight monkeys (Macaca mulatta), and levels of t-MH and t-MIAA were measured by gas chromatography-mass spectrometry. pros-Methylimidazoleacetic acid (p-MIAA), an endogenous isomer of t-MIAA that is not a histamine metabolite, was also measured. Cisternal levels (in picomoles per milliliter, mean +/- SEM) of t-MH (9.9 +/- 1.4) and t-MIAA (40.8 +/- 7.6), but not of p-MIAA (9.7 +/- 1.2), exceeded those in lumbar CSF (t-MH, 1.8 +/- 0.3; t-MIAA, 6.8 +/- 0.9; p-MIAA, 8.6 +/- 0.6) in every monkey. The magnitudes of the mean cisternal-lumbar concentration gradients for t-MH (6.6 +/- 1.1) and t-MIAA (6.5 +/- 1.3) were indistinguishable. These gradients exceed those of metabolites of most other transmitters. There was no gradient for the levels of p-MIAA. The cisternal, but not lumbar, levels of t-MH and t-MIAA were correlated. There was no significant difference between the means of the metabolite concentration ratios (t-MIAA/t-MH) in cisternal (4.0 +/- 0.4) and lumbar (4.4 +/- 0.9) CSF. The steepness of these gradients suggests that levels of t-MH and t-MIAA in lumbar CSF might be useful probes of histaminergic metabolism in brain.
与其他胺能递质的代谢产物类似,脑内组胺的代谢产物——3-甲基组胺(t-MH)和3-甲基咪唑乙酸(t-MIAA),在脑脊液的头端和尾端部位之间可能存在浓度梯度。为了验证这一假设,从8只猕猴(恒河猴)成对采集了枕大池和腰段脑脊液样本,并通过气相色谱-质谱法测量了t-MH和t-MIAA的水平。还测量了t-MIAA的内源性异构体——前体-甲基咪唑乙酸(p-MIAA),它不是组胺代谢产物。每只猴子枕大池脑脊液中t-MH(9.9±1.4)和t-MIAA(40.8±7.6)的水平(皮摩尔/毫升,平均值±标准误)超过了腰段脑脊液中的水平(t-MH,1.8±0.3;t-MIAA,6.8±0.9;p-MIAA,8.6±0.6),但p-MIAA除外。t-MH(6.6±1.1)和t-MIAA(6.5±1.3)的平均枕大池-腰段浓度梯度大小无明显差异。这些梯度超过了大多数其他递质代谢产物的梯度。p-MIAA水平无梯度。t-MH和t-MIAA的枕大池水平相关,但腰段水平不相关。枕大池脑脊液(4.0±0.4)和腰段脑脊液(4.4±0.9)中代谢产物浓度比(t-MIAA/t-MH)的平均值之间无显著差异。这些梯度的陡峭程度表明,腰段脑脊液中t-MH和t-MIAA的水平可能是脑内组胺能代谢的有用探针。