Reinhold Stephan W, Vitzthum Helga, Filbeck Thomas, Wolf Konrad, Lattas Christos, Riegger Günter A J, Kurtz Armin, Krämer Bernhard K
Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany.
Am J Physiol Renal Physiol. 2006 Apr;290(4):F864-72. doi: 10.1152/ajprenal.00169.2005. Epub 2005 Oct 11.
The arachidonate signaling pathways comprise prostanoids formed by cyclooxygenases, EETs, and HETEs formed by cytochrome P-450 (CYP) enzymes and HETEs and leukotrienes generated by lipoxygenases. Whereas the intrarenal localization of cyclooxygenases and of some CYP enzymes along the nephron has already been determined, the localization of lipoxygenases and leukotriene-forming enzymes together with leukotriene receptors in the kidney is less clear. This study therefore aimed to determine the expression of 5-, 12-, and 15-lipoxygenases as well as the leukotriene receptors along the rat nephron. The kidneys were dissected into cortex and outer and inner medulla, and the microdissected nephron segments were collected after a collagenase digestion. mRNA abundance was determined by RT-PCR and real-time PCR. 15-LOX mRNA showed a characteristic expression pattern along the distal nephron. 12-LOX mRNA was only found in the glomerulus. Similarly, 5-LOX mRNAs together with 5-LOX-activating protein mRNAs were expressed in the glomerulus and also in the vasa recta. The leukotriene A4 hydrolase was found in all nephron segments, whereas leukotriene C4 synthase mRNA could not be found in any nephron segment. The leukotriene receptor B4 and the cysteinyl leukotriene receptor type 1 were selectively expressed in the glomerulus, whereas cysteinyl receptor type 2 was not found in any nephron segment. Our data suggest that the glomerulus is a major source and target for 5- and 12-HETE and for leukotrienes. The collecting duct system, on the other hand, appears to be a major source of 15-HETE.
花生四烯酸信号通路包括由环氧化酶形成的前列腺素、由细胞色素P-450（CYP）酶形成的环氧二十碳三烯酸（EETs）和羟二十碳四烯酸（HETEs），以及由脂氧合酶产生的HETEs和白三烯。虽然环氧化酶和一些CYP酶在肾单位中的肾内定位已经确定，但脂氧合酶和白三烯形成酶以及白三烯受体在肾脏中的定位尚不清楚。因此，本研究旨在确定大鼠肾单位中5-、12-和15-脂氧合酶以及白三烯受体的表达情况。将肾脏解剖为皮质、外髓和内髓，胶原酶消化后收集显微解剖的肾单位节段。通过逆转录聚合酶链反应（RT-PCR）和实时聚合酶链反应（real-time PCR）测定mRNA丰度。15-脂氧合酶（15-LOX）mRNA沿远端肾单位呈现特征性表达模式。12-LOX mRNA仅在肾小球中发现。同样，5-LOX mRNA与5-LOX激活蛋白mRNA在肾小球和直小血管中均有表达。白三烯A4水解酶在所有肾单位节段中均有发现，而在任何肾单位节段中均未发现白三烯C4合酶mRNA。白三烯受体B4和半胱氨酰白三烯受体1型在肾小球中选择性表达而半胱氨酰受体2型在任何肾单位节段中均未发现。我们的数据表明，肾小球是5-和12-HETE以及白三烯的主要来源和靶点。另一方面，集合管系统似乎是15-HETE的主要来源。
