Metabolism of cysteinyl leukotrienes in non-recirculating rat liver perfusion. Hepatocyte heterogeneity in uptake and biliary excretion.
Metabolism of cysteinyl leukotrienes in non-recirculating rat liver perfusion. Hepatocyte heterogeneity in uptake and biliary excretion.
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非再循环大鼠肝脏灌注中半胱氨酰白三烯的代谢。
DOI：
10.1111/j.1432-1033.1989.tb14701.x
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
D. Häussinger
中科院分区：
文献类型：
--
作者：
M. Wettstein;Wolfgang Gerok;D. Häussinger
1.在非再循环大鼠肝脏灌注系统中，在顺行（从门静脉到腔静脉）和逆行（从腔静脉到门静脉）灌注方向的恒定流量下，研究了半胱氨酰白三烯LTC4、LTD4和LTE4的摄取、代谢和胆汁排泄。在顺行灌注中输注[3H] LTC 4、[3H] LTD 4和[3H] LTE 4（各10 nmol/l）5 min期间，灌注液中放射性的单程提取率分别为66%、81%和83%。在逆行灌注中相应的LTC4和LTD4值分别为83%和93%，表明逆行灌注中半胱氨酰白三烯的摄取比顺行灌注更有效。流出液灌注液中未代谢的白三烯浓度在顺行灌注中为8 - 12%，在逆行灌注中为2 - 4%。[14C]从灌注液中提取的牛磺胆酸盐仅被LTC4抑制3%，这表明门静脉/肝静脉分流的打开不能解释灌注方向对肝脏LTC4摄取的影响。2.在顺行灌注方向输注[3H] LTC 4和[3H] LTD 4后，分别约80%和87%的被肝脏吸收的放射性标记被排泄到胆汁中。然而，在逆行灌注中，分别只有40%和57%被排泄到胆汁中，其余的被缓慢地重新分配到灌注液中，表明白三烯被吸收到肝隔室中，胆汁清除效果较差，或转化为逃避胆汁排泄的代谢物。胆汁中发现的代谢物模式不受灌注方向的影响。除了未修饰的LTC4（17 - 18%）外，LTC4的胆汁产物为极性代谢产物（31 - 38%）、LTD 4（27 - 30%）、LTE 4（约1%）和N-乙酰基-LTE 4（3 - 4%）。3. LTC4被鉴定为胆汁中[3H] LTD 4的主要代谢产物，约占排泄至胆汁中的总放射性的20%。这可能是由于γ-谷氨酰转移酶催化的谷氨酰从胆汁室中的谷胱甘肽转移，如体外实验所示。在灌注的大鼠肝脏中存在正弦γ-谷氨酰转移酶活性，在注入的γ-谷氨酰-对硝基苯胺的水解实验中显示。AT-125对该酶活性的90%抑制不影响LTC4的代谢。4.当[3H] LTE4以顺行灌注方向输注时，胆汁代谢物包括N-乙酰基-LTE4（24%）和极性组分（60%）。（400字处截断摘要）
1. The uptake, metabolism and biliary excretion of the cysteinyl leukotrienes LTC4, LTD4 and LTE4, were studied in a non-recirculating rat liver perfusion system at constant flow in both antegrade (from the portal to the caval vein) and retrograde (from the caval to the portal vein) perfusion directions. During a 5-min infusion of [3H]LTC4, [3H]LTD4 and [3H]LTE4 (10 nmol/l each) in antegrade perfusions single-pass extractions of radioactivity from the perfusate were 66%, 81% and 83%, respectively. Corresponding values for LTC4 and LTD4 in retrograde perfusions were 83% and 93%, respectively, indicating a more efficient uptake of cysteinyl leukotrienes in retrograde than in antegrade perfusions. The concentrations of unmetabolized leukotrienes in the effluent perfusate were 8-12% in antegrade and 2-4% in retrograde perfusions. [14C]Taurocholate extraction from the perfusate was inhibited by LTC4 by only 3%, suggesting that an opening of portal-venous/hepatic-venous shunts does not explain the effects of perfusion direction on hepatic LTC4 uptake. 2. Following infusion of [3H]LTC4 and [3H]LTD4, in the antegrade perfusion direction, about 80% and 87%, respectively, of the radiolabel taken up by the liver was excreted into bile. In retrograde perfusions, however, only 40% and 57%, respectively, was excreted into bile and the remainder was slowly redistributed into the perfusate, indicating that leukotrienes were taken up into a hepatic compartment with less effective biliary elimination or converted to metabolites escaping biliary excretion. The metabolite pattern found in bile was not affected by the direction of perfusion. Biliary products of LTC4 were polar metabolites (31-38%), LTD4 (27-30%), LTE4 (about 1%) and N-acetyl-LTE4 (3-4%) in addition to unmodified LTC4 (17-18%). 3. LTC4 was identified as a major metabolite of [3H]LTD4 in bile, amounting to about 20% of the total radioactivity excreted into bile. This is probably due to a gamma-glutamyltransferase-catalyzed glutamyl transfer from glutathione in the biliary compartment, as demonstrated in in vitro experiments. The presence of sinusoidal gamma-glutamyltransferase activity in perfused rat liver was shown in experiments on the hydrolysis of infused gamma-glutamyl-p-nitroanilide. 90% inhibition of this enzyme activity by AT-125 did not affect the metabolism of LTC4. 4. When [3H]LTE4 was infused in the antegrade perfusion direction, biliary metabolites comprised N-acetyl-LTE4 (24%) and polar components (60%).(ABSTRACT TRUNCATED AT 400 WORDS)
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DOI：
10.1016/s0021-9258(19)57482-8
发表时间：
1986-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
N. Ballatori;R. Jacob;J. Boyer
通讯作者：
N. Ballatori;R. Jacob;J. Boyer
白三烯 E4 在离体大鼠肝细胞中的代谢。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Stene,DO;Murphy,RC
通讯作者：
Murphy,RC
白三烯 C4 和组胺在人体过敏性皮肤反应中的积累。
DOI：
10.1172/jci112018
发表时间：
1985
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Talbot,SF;Atkins,PC;Goetzl,EJ;Zweiman,B
通讯作者：
Zweiman,B
胎儿和新生大鼠肝脏中γ-谷氨酰转肽酶活性的消失模式和速率。
DOI：
10.1177/31.11.6194205
发表时间：
1983
期刊：
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
影响因子：
--
作者：
Iannaccone,PM;Koizumi,J
通讯作者：
Koizumi,J
白三烯 C 和 D 结构类似物的收缩活性：极性取代基的作用。
DOI：
10.1073/pnas.78.7.4579
发表时间：
1981
影响因子：
11.1
作者：
Lewis,RA;Drazen,JM;Austen,KF;Toda,M;Brion,F;Marfat,A;Corey,EJ
通讯作者：
Corey,EJ