Lee Y C, Allen J M, Uttenthal L O, Walker M C, Shemilt J, Gill S S, Bloom S R
J Clin Endocrinol Metab. 1984 Jul;59(1):45-50. doi: 10.1210/jcem-59-1-45.
The metabolism of iv infused neurotensin (NT) was studied and its disappearance half-time compared with that of infused N-terminal octapeptide of NT 1-8 in six normal subjects by RIA with antisera directed against the C- and N-terminal regions of the NT molecule. The disappearance half-time of NT in circulating plasma was 1.4 min measured with the C-terminal antibody and 6.0 min measured with the N-terminal antibody. The disappearance half-time of NT 1-8 was 30 min measured with the N-terminal antibody. Gel filtration and high pressure liquid chromatographic analysis indicated that a substantial amount of immunoreactive NT in the plasma of subjects infused with synthetic NT was eluted at the NT 1-8 position and a lesser amount of plasma NT-like immunoreactivity was eluted with synthetic NT. These findings suggest that NT is readily metabolized in the circulation to NT 1-8. A significant rise in the mean plasma concentration of pancreatic polypeptide was produced by NT, but not by NT 1-8, infused at 2.4 pmol kg-1 min-1. No changes in the mean plasma concentrations of insulin, glucose, or cholesterol were demonstrated during either infusion. The present study suggests that the rapid degradation of NT in man to its N-terminal metabolite may be one of the mechanisms for its bioinactivation in plasma.
通过使用针对神经降压素（NT）分子C端和N端区域的抗血清进行放射免疫分析（RIA），在六名正常受试者中研究了静脉输注NT的代谢情况，并将其消失半衰期与输注的NT 1-8 N端八肽的消失半衰期进行了比较。用C端抗体测得循环血浆中NT的消失半衰期为1.4分钟，用N端抗体测得为6.0分钟。用N端抗体测得NT 1-8的消失半衰期为30分钟。凝胶过滤和高压液相色谱分析表明，在输注合成NT的受试者血浆中，大量免疫反应性NT在NT 1-8位置被洗脱，而较少的血浆NT样免疫反应性与合成NT一起被洗脱。这些发现表明，NT在循环中很容易代谢为NT 1-8。以2.4 pmol kg-1 min-1的速率输注NT可使胰多肽的平均血浆浓度显著升高，但输注NT 1-8则不会。在任何一种输注过程中，胰岛素、葡萄糖或胆固醇的平均血浆浓度均未显示出变化。本研究表明，人类体内NT迅速降解为其N端代谢产物可能是其在血浆中生物失活的机制之一。
