Lu C L, Chan J S, De Léan A, Chen A, Seidah N G, Chrétien M
Life Sci. 1983 Dec 26;33(26):2599-608. doi: 10.1016/0024-3205(83)90343-0.
In metabolic clearance rate (MCR) and plasma half-time disappearance rate (t 1/2) of human N-terminal (1-76) and adrenocorticotropin(hACTH 1-39) of pro-opiomelanocortin were compared after intravenous bolus injection of both peptides simultaneously into rat. The level of immunoreactive (IR) hNT and IR-ACTH in plasma and urine samples were measured by specific and homologous radioimmunoassays (RIAs). The MCR and hNT and hACTH were 3.01 +/- 0.20 ml/min (M +/- S.D., N = 4) and 2.04 +/- 0.06 ml/min, respectively (p less than 0.05), The curve for the disappearance rate of IR-hNT was triphasic (rapid t 1/2 = 0.96 +/- 0.39 min, intermediate t 1/2 = 6.7 +/- 2.25 min, and slow t 1/2 = 74 +/- 15.8 min), while that of IR-ACTH was biphasic (rapid t 1/2 = 3.3 +/- 0.68 min, and slow t 1/2 = 41.5 +/- 3.03 min) as analyzed by the non-linear least-squares methods. Statistically significant difference (p less than 0.01) was found between IR-hNT and IR-hACTH in the rapid t 1/2 and in the slow t 1/2. Subsequent analysis of pooled plasma sample (30 min post-injection) by molecular sieve chromatography on Sephadex G-50 superfine column revealed that the majority of IR-hNT (90-95%) and IR-ACTH (60-70%) are co-chromatographed with [125I]iodo hNT and [125I]iodo ACTH respectively. Similarly, gel filtration of pooled urine sample (120 min post-injection) on Sephadex G-50 superfine revealed that 80-90% of IR-hNT and less than 50% of IR-ACTH co-eluted with [125I]iodo hNT and [125I]iodo ACTH, respectively. Smaller molecular forms of IR-hNT and IR-ACTH were definitely apparent in the urine sample. In conclusion, hNT has a larger MCR and a longer half-time disappearance rate (t 1/2) than IR-hACTH in rat plasma and it appears that hNT is more resistant to degradation by plasma and by kidney than hACTH.
将人阿片促黑激素原的N端（1 - 76）和促肾上腺皮质激素（hACTH 1 - 39）同时静脉推注到大鼠体内后，比较了二者的代谢清除率（MCR）和血浆半衰期消失率（t1/2）。通过特异性和同源放射免疫分析法（RIAs）测定血浆和尿液样本中免疫反应性（IR）hNT和IR - ACTH的水平。hNT和hACTH的MCR分别为3.01±0.20 ml/min（M±S.D.，N = 4）和2.04±0.06 ml/min（p < 0.05）。IR - hNT消失率曲线为三相（快速t1/2 = 0.96±0.39 min，中间t1/2 = 6.7±2.25 min，缓慢t1/2 = 74±15.8 min），而IR - ACTH消失率曲线为双相（快速t1/2 = 3.3±0.68 min，缓慢t1/2 = 41.5±3.03 min），采用非线性最小二乘法分析。在快速t1/2和缓慢t1/2时，IR - hNT和IR - ACTH之间存在统计学显著差异（p < 0.01）。随后，在Sephadex G - 50超细柱上对注射后30分钟的混合血浆样本进行分子筛层析分析，结果显示大部分IR - hNT（90 - 95%）和IR - ACTH（60 - 70%）分别与[125I]碘hNT和[125I]碘ACTH共层析。同样，在Sephadex G - 50超细柱上对注射后120分钟的混合尿液样本进行凝胶过滤分析，结果显示80 - 90%的IR - hNT和不到50%的IR - ACTH分别与[125I]碘hNT和[125I]碘ACTH共洗脱。在尿液样本中，IR - hNT和IR - ACTH的较小分子形式明显可见。总之，在大鼠血浆中，hNT的MCR比IR - hACTH大，半衰期消失率（t1/2）更长，而且hNT似乎比hACTH更耐血浆和肾脏的降解。
