Rinkema L E, Roman C R, VanAlstyne E L, Spaethe S M, Fleisch J H
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Naunyn Schmiedebergs Arch Pharmacol. 1993 Nov;348(5):520-5. doi: 10.1007/BF00173213.
Guinea pig inferior vena cava contracted in response to leukotriene (LT)C4, LTD4, LTE4 U46619, phenylephrine, histamine, and KCl. Although LTC4, LTD4, and U46619 were the most potent agonists, active tension generated by these eicosanoids was only about half that of histamine or KCl. LTE4 and phenylephrine were marginally active. Biochemical analysis showed vena cava able to convert about 23% LTC4 to LTD4 and LTE4 in 45 min. Pretreatment with acivicin prevented this by abrogating conversion of LTC4 to LTD4. A subthreshold concentration of LTE4 reduced responses to LTC4 and LTD4. LY171883 and WY-48252 competitively antagonized LTD4-induced contractions of vena cava. In contrast, these antagonists blocked contractions to LTC4 in a biphasic manner. Lower segments of the LTC4 concentration-response curves were less affected than the upper portion suggesting the possibility of 2 LTC4 receptor subtypes. Our results indicate that LTE4 is a weak or partial agonist in this tissue and furthermore they suggest a lack of high affinity receptors for LTE4 favoring LTC4 and LTD4. Indomethacin did not influence contractions to the leukotrienes or histamine. However, the response to U46619 was greatly enhanced suggesting release of a vasodilator prostaglandin as part of the overall response of the vena cava to the thromboxane A2 mimetic.
豚鼠下腔静脉对白三烯（LT）C4、LTD4、LTE4、U46619、去氧肾上腺素、组胺和氯化钾产生收缩反应。尽管LTC4、LTD4和U46619是最有效的激动剂，但这些类花生酸产生的主动张力仅约为组胺或氯化钾的一半。LTE4和去氧肾上腺素的活性较弱。生化分析表明，下腔静脉在45分钟内能够将约23%的LTC4转化为LTD4和LTE4。阿西维辛预处理通过消除LTC4向LTD4的转化来阻止这种情况。亚阈值浓度的LTE4降低了对LTC4和LTD4的反应。LY171883和WY - 48252竞争性拮抗LTD4诱导的下腔静脉收缩。相比之下，这些拮抗剂以双相方式阻断对LTC4的收缩。LTC4浓度 - 反应曲线的下段受影响小于上段，提示可能存在2种LTC4受体亚型。我们的结果表明，LTE4在该组织中是一种弱激动剂或部分激动剂，此外，这表明缺乏对LTE4的高亲和力受体，而更倾向于LTC4和LTD4。吲哚美辛不影响对白三烯或组胺的收缩反应。然而，对U46619的反应大大增强，提示作为下腔静脉对血栓素A2模拟物整体反应的一部分，有血管舒张性前列腺素的释放。
