Pedersen J H, Andersen H O, Olsen P S, Henriksen J H
Department of Surgery C, Rigshospitalet, Copenhagen, Denmark.
J Clin Endocrinol Metab. 1989 Feb;68(2):294-300. doi: 10.1210/jcem-68-2-294.
We studied the pharmacokinetics, arteriovenous extraction, and degradation sites of neurotensin (NT) in man during iv infusions of synthetic intact NT [NT-(1-13)] and the NH2-terminal metabolite NT-(1-8) during lipid ingestion and by catheterization of various vascular beds in normal subjects and patients with hepatic disease. NT-like immunoreactivities in plasma were quantitated using 2 sequence-specific RIAs and gel filtration chromatography. During iv infusion of NT-(1-13) in 6 normal subjects, the median t1/2 was 1.7 min (interquartile range, 0.7-2.8), the MCR was 36 mL/kg.min (range, 21-54), and distribution space was 78.8 mL/kg (range, 56-91). The results were similar at infusion rates of 72, 144, and 288 pmol/kg.h (n = 6). During infusion of NT-(1-8) in 7 normal subjects, the median t1/2 was 8.3 min (range, 4.7-13.8), the MCR was 11.0 mL/kg.min (range, 6.7-21.7), and the distribution space was 142.6 mL/kg (range, 45.3-281.0). Significant peripheral arteriovenous extraction of NT-(1-13) was found at infusion rates of 144 and 288 pmol/kg.h. Extraction of NH2-terminal immunoreactivity was not significant. Intact NT was identified by gel chromatography in arterial plasma after lipid ingestion and iv infusion of NT-(1-13), but postprandially in only low concentrations. In 17 patients with various nonhepatic diseases, plasma intact NT levels were not different in blood sampled from the renal vein, inferior vena cava, brachial artery, or hepatic vein. In contrast, NH2-terminal immunoreactivity was significantly higher in hepatic venous than in systemic plasma. In 6 patients with hepatic disease, systemic plasma intact NT levels were increased, but even more so in hepatic venous plasma. These results demonstrate that metabolism of intact NT is rapid, and a significant peripheral arterio-venous extraction is present. Further studies are necessary to establish if the liver is a site of degradation of intact NT in man.
我们在正常受试者和肝病患者中，通过脂质摄入期间静脉输注合成的完整神经降压素[NT-(1-13)]和氨基末端代谢产物NT-(1-8)，以及对各种血管床进行插管，研究了神经降压素（NT）在人体中的药代动力学、动静脉摄取和降解部位。使用两种序列特异性放射免疫分析法和凝胶过滤色谱法定量血浆中的NT样免疫反应性。在6名正常受试者静脉输注NT-(1-13)期间，中位半衰期为1.7分钟（四分位间距，0.7 - 2.8），代谢清除率为36 mL/kg·min（范围，21 - 54），分布容积为78.8 mL/kg（范围，56 - 91）。在72、144和288 pmol/kg·h的输注速率下结果相似（n = 6）。在7名正常受试者静脉输注NT-(1-8)期间，中位半衰期为8.3分钟（范围，4.7 - 13.8），代谢清除率为11.0 mL/kg·min（范围，6.7 - 21.7），分布容积为142.6 mL/kg（范围，45.3 - 281.0）。在144和288 pmol/kg·h的输注速率下发现NT-(1-13)有显著的外周动静脉摄取。氨基末端免疫反应性的摄取不显著。在脂质摄入和静脉输注NT-(1-13)后，通过凝胶色谱法在动脉血浆中鉴定出完整的NT，但餐后浓度仅较低。在17例患有各种非肝病的患者中，从肾静脉、下腔静脉、肱动脉或肝静脉采集的血液中血浆完整NT水平无差异。相反，肝静脉中的氨基末端免疫反应性明显高于全身血浆。在6例肝病患者中，全身血浆完整NT水平升高，但肝静脉血浆中升高更明显。这些结果表明完整NT的代谢迅速，且存在显著的外周动静脉摄取。有必要进一步研究以确定肝脏是否是人体中完整NT的降解部位。
