Seno M, Seino Y, Takemura Y, Nishi S, Ishida H, Kitano N, Imura H, Taminato T, Matsukura S
Can J Physiol Pharmacol. 1985 Jan;63(1):62-7. doi: 10.1139/y85-011.
The hepatic clearances of somatostatin (SS)-28 and SS-14 by the perfused rat liver were compared, using a recirculating, plasma-free, erythrocyte-containing perfusion system. The disappearance rate constant, half time, clearance, and hepatic extraction ratio when 1.2 nM SS-28 was added to the perfusate were 0.0221 +/- 0.0051 min-1, 36.6 +/- 7.6 min, 0.34 +/- 0.08 mL/min, and 17.2 +/- 3.9%, respectively. The corresponding values obtained when SS-14 was added to the perfusate were 0.0405 +/- 0.0022 min-1, 17.3 +/- 1.0 min, 0.71 +/- 0.05 mL/min, and 35.4 +/- 2.6%, respectively. The differences between the SS-28 and SS-14 indices were all statistically significant. In addition, the perfusates with SS-28 added were eluted on Sephadex G-25 fine columns and somatostatinlike immunoreactivity (SLI) was determined. No SS-14 was found in perfusate containing SS-28 at both 5 and 30 min after the beginning of the perfusion. To investigate whether or not the liver plays an important role in the clearance of SS-28 or the conversion of SS-14 in vivo, the plasma disappearance of 2 micrograms SS-28 was compared in the whole rat and the functionally hepatectomized model. The half time of plasma SS-28 was 1.43 +/- 0.12 min in the whole rat, significantly shorter than the 2.20 +/- 0.14 min in the hepatectomized model. Gel filtration of plasma extract samples at 0.5 min after the SS-28 injection showed two major peaks of SLI: a first peak corresponding to SS-28 and a second peak coeluted in the position of SS-14 in both the whole rat and the hepatectomized model. At 4 min after the SS-28 injection, the first peak disappeared and only a small second peak was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
使用循环、无血浆、含红细胞的灌注系统,比较了灌注大鼠肝脏对生长抑素(SS)-28和SS-14的肝清除率。当向灌注液中加入1.2 nM SS-28时,其消失速率常数、半衰期、清除率和肝提取率分别为0.0221±0.0051 min⁻¹、36.6±7.6 min、0.34±0.08 mL/min和17.2±3.9%。当向灌注液中加入SS-14时,相应的值分别为0.0405±0.0022 min⁻¹、17.3±1.0 min、0.71±0.05 mL/min和35.4±2.6%。SS-28和SS-14各项指标之间的差异均具有统计学意义。此外,将添加了SS-28的灌注液在Sephadex G-25细柱上洗脱,并测定生长抑素样免疫反应性(SLI)。在灌注开始后5分钟和30分钟时,含SS-28的灌注液中均未发现SS-14。为研究肝脏在体内对SS-28的清除或SS-14的转化中是否起重要作用,比较了全大鼠和功能性肝切除模型中2微克SS-28的血浆消失情况。全大鼠血浆中SS-28的半衰期为1.43±0.12分钟,显著短于肝切除模型中的2.20±0.14分钟。在注射SS-28后0.5分钟对血浆提取物样品进行凝胶过滤,显示出两个主要的SLI峰:第一个峰对应SS-28,第二个峰在全大鼠和肝切除模型中均与SS-且在SS-14的位置共洗脱。在注射SS-28后4分钟,第一个峰消失,仅观察到一个小的第二个峰。