Taylor I K, O'Malley G, Murray S, Turner N, Taylor G W, Fuller R W, Pride N, Dollery C T
Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
J Appl Physiol (1985). 1990 Aug;69(2):591-6. doi: 10.1152/jappl.1990.69.2.591.
N tau-methylimidazole acetic acid (N tau-MIAA) is the principal urinary metabolite of histamine. The basal urinary excretion rate of N tau-MIAA was determined as 0.117 +/- 0.008 (SE) mg/h, with a renal clearance for N tau-MIAA of 273 +/- 27 ml/min implying active secretion. After subpharmacological infusion of histamine (50 ng.kg-1.min-1 over 2 h) in five volunteers that increased plasma histamine from 0.28 +/- 0.04 to 0.71 +/- 0.15 ng/ml, urinary excretion of N tau-MIAA over 8 h was increased by less than 17% compared with a control saline infusion. Urinary N tau-MIAA excretion in normal controls (273 +/- 14 micrograms/mmol creatinine) was similar to that observed in patients with severe acute asthma (253 +/- 22 micrograms/mmol), antigen-induced bronchoconstriction (269 +/- 21 micrograms/mmol), seasonal allergic rhinitis (304 +/- 31 micrograms/mmol), and clinically stable bronchiectasis (270 +/- 22 micrograms/mmol). In contrast, large increases in metabolite excretion (greater than 7,000 micrograms/mmol creatinine) were observed in a patient with systemic mastocytosis where very high plasma histamine levels were recorded (greater than 500 ng/ml) and marked systemic hemodynamic effects occurred. We conclude that urinary N tau-MIAA will only be increased in pathologies where sustained hyperhistaminemia occurs and that increased local histamine production in the lung or the upper airway does not cause a measurable change in the basal urinary excretion of this metabolite.
N-τ-甲基咪唑乙酸(N-τ-MIAA)是组胺的主要尿代谢产物。N-τ-MIAA的基础尿排泄率测定为0.117±0.008(标准误)mg/h,N-τ-MIAA的肾清除率为273±27 ml/min,提示存在主动分泌。在5名志愿者中进行亚药理剂量的组胺输注(2小时内50 ng·kg⁻¹·min⁻¹),使血浆组胺水平从0.28±0.04 ng/ml升高至0.71±0.15 ng/ml,与生理盐水对照输注相比,8小时内N-τ-MIAA的尿排泄量增加不到17%。正常对照者的尿N-τ-MIAA排泄量(273±14μg/mmol肌酐)与重症急性哮喘患者(253±22μg/mmol)、抗原诱导的支气管收缩患者(269±21μg/mmol)、季节性变应性鼻炎患者(304±31μg/mmol)及临床稳定的支气管扩张患者(270±22μg/mmol)相似。相比之下,在一名系统性肥大细胞增多症患者中观察到代谢产物排泄量大幅增加(大于7000μg/mmol肌酐),该患者血浆组胺水平极高(大于500 ng/ml)且出现明显的全身血流动力学效应。我们得出结论,仅在发生持续性高组胺血症的病理状态下尿N-τ-MIAA才会升高,且肺或上呼吸道局部组胺产生增加不会导致该代谢产物基础尿排泄量出现可测量的变化。