CLEARANCE STUDIES OF OXYTOCIN IN HUMANS USING RADIOIMMUNOASSAY MEASUREMENTS OF THE HORMONE IN PLASMA AND URINE

CLEARANCE STUDIES OF OXYTOCIN IN HUMANS USING RADIOIMMUNOASSAY MEASUREMENTS OF THE HORMONE IN PLASMA AND URINE
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DOI:
10.1210/jcem-64-2-340
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发表时间:
1987-02-01
影响因子:
5.8
通讯作者:
ROBINSON, AG
ROBINSON, AG
中科院分区:
医学2区
文献类型:
--
作者:
AMICO, JA;ULBRECHT, JS;ROBINSON, AG

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合成催产素(OT)以3 mU/min的速度静脉输注给4名男性,每90分钟输注速率加倍,共输注3次。平均值(.+-. SEM)OT MCR为16.4 ±-。1.7 ml/kg·cntdot. min,与输注速率无关。建立了一种用十八烷基硅胶柱提取尿中催产素的方法。将提取的残留物在磷酸钾缓冲液(pH 7.4)中复溶,用于RIA。尿中OT的最低可检测水平为0.2 μ U/ml(定义为结合与游离的比率为apx。90%)。OT的平均回收率为77 ± 0.9%。百分之二平均值(.+-. SEM)尿中内源性OT浓度为10.2 ± 0.001。1.4μ U/ml。尿中的内源性OT从反相高压液相色谱柱洗脱,在合成OT的位置上作为OT免疫反应性的单峰。合成OT输注过程中尿OT排泄与血浆OT浓度呈线性相关,无论是以尿OT/mg肌酐微单位(r = 0.89)还是尿OT/min(r = 0.93)计算。OT的平均尿清除率分数(OT清除率/肌酐清除率)为OT的3.6%肾清除率(5.5 ml/min或MCR的0.43%)。因此,OT MCR在很宽的生理血浆OT水平范围内是恒定的,并且与本实验室先前研究的妊娠女性中的MCR相似。不到1%的OT在尿液中被清除。本研究定义了在稳态输注生理浓度的激素过程中尿和血浆OT之间的关系,并表明通过RIA测量尿中的OT可能有助于人体OT相关事件的药代动力学和生理学研究。
Synthetic oxytocin (OT) was infused Iv in four men at 3 mU/min, and the rate was doubled every 90 min for a total of three infusion periods. The mean ( .+-. SEM) OT MCR was 16.4 .+-. 1.7 ml/kg .cntdot. min and was independent of the rate of infusion. A method for measuring OT in urine was developed using an octadecasilyl-silica column for extraction of the hormone. The extracted residue was reconstituted in potassium phosphate buffer, pH 7.4, for RIA. The minimum detectable level of OT in urine was 0.2 .mu.U/ml (defined as a bound to free ratio of .apprx. 90%). The mean recovery of OT was 77 .+-. 2%. The mean ( .+-. SEM) concentration of endogenous OT in urine was 10.2 .+-. 1.4 .mu.U/ml. Endogenous OT in urine eluted from a reverse phase high pressure liquid chromatography column as a single peak of OT immunoreactivity in the position of synthetic OT. Urinary OT excretion during infusion of synthetic OT was linearly correlated with plasma OT concentration whether calculated as microunits of urinary OT per mg creatinine (r = 0.89) or urinary OT per min (r = 0.93). Mean urinary fractional clearance of OT (OT clearance/creatinine clearance) was 3.6% renal clearance of OT (5.5 ml/min or 0.43% of MCR). Thus, OT MCR was constant over a wide range of physiological plasma OT levels and was similar to MCR in pregnant women studied previously in this laboratory. Less than 1% of OT was cleared in urine. This study defines the relationship between urinary and plasma OT during steady state infusion of physiological concentrations of the hormone and indicates that measurements of OT in urine by RIA may prove helpful for pharmacokinetic and physiological studies of OT-related events in humans.