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二磺酸芪(SITS)在灌注豚鼠肝脏中的摄取与作用:与磺溴酞的比较。

Uptake and action of a disulphonic stilbene (SITS) in the perfused guinea-pig liver: a comparison with bromsulphthalein.

作者信息

Rutishauser S C

出版信息

J Physiol. 1983 Jan;334:505-18. doi: 10.1113/jphysiol.1983.sp014509.

Abstract
  1. Livers were perfused with a Krebs-Ringer bicarbonate buffer in a single-pass perfusion system. Bile secretion was maintained by infusion of secretin. 4-Acetamido-4'-isothiocyano-2,2'-stilbene disulphonic acid (SITS) was added to the perfusate to give concentrations ranging between 5 x 10(-6) and 10(-4) M. 2. SITS was extracted from the perfusate by the liver (V, 0 . 15 mumol/min per g liver; Km 8 . 6 x 10(-5) M) and excreted in bile in a modified form (bile/plasma ratio: 50-170; maximum rate of excretion: 25 nmol/min per g liver wet wt). 3. The rates of uptake and excretion of bromsulphthalein (BSP) were similar to those for SITS, with the exception that the affinity of BSP for hepatic uptake was greater (Km 1 . 8 x 10(-5) M). 4. Both SITS and BSP decreased the rate of bile flow. A 50% reduction in bile flow was attained in each case at an estimated drug content of the liver of 1 . 5 mumol/g wet wt. 5. Unlike other cells the hepatocyte appears to be readily penetrated by SITS, and it is suggested that SITS inhibits bile secretion by inhibiting an intracellular mechanism which could be mitochondrial in location.
摘要
  1. 在单通道灌注系统中,用 Krebs-Ringer 碳酸氢盐缓冲液灌注肝脏。通过输注促胰液素维持胆汁分泌。向灌注液中加入 4-乙酰氨基-4'-异硫氰基-2,2'-二苯乙烯二磺酸(SITS),使其浓度在 5×10⁻⁶至 10⁻⁴M 之间。

  2. SITS 被肝脏从灌注液中摄取(V,每克肝脏 0.15 μmol/分钟;Km 8.6×10⁻⁵M),并以修饰形式排泄到胆汁中(胆汁/血浆比率:50 - 170;最大排泄速率:每克肝脏湿重 25 nmol/分钟)。

  3. 溴磺酞钠(BSP)的摄取和排泄速率与 SITS 相似,不同之处在于 BSP 对肝脏摄取的亲和力更高(Km 1.8×10⁻⁵M)。

  4. SITS 和 BSP 均降低胆汁流速。在每种情况下,当肝脏中药物含量估计为 1.5 μmol/g 湿重时,胆汁流速降低 50%。

  5. 与其他细胞不同,肝细胞似乎很容易被 SITS 穿透,提示 SITS 通过抑制一种可能位于线粒体的细胞内机制来抑制胆汁分泌。

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