CORNEAL ARACHIDONATE METABOLITES VIA CYTOCHROME P450

角膜的上皮细胞层可以被描述为 “紧密”离子转运功能合胞体，既是 一种保护眼表的屏障，作为一种辅助液体- 协助角膜内皮调节的分泌层 基质水合作用，因此，有助于 保持角膜的透明度。的传输特性 角膜上皮细胞与角膜上皮细胞相似。 亨勒氏环(TALH)的粗大升支，即肾单位 对于建立溶质梯度很重要的一段 尿液浓度通过氯化钠耦合转运。 两种转运上皮均具有活跃的氯离子转运偶联 至Na+-K+激活的ATPase。最近，我们报道了 TALH通过细胞色素代谢花生四烯酸 P450依赖酶(S)对两种生物活性代谢物的作用： 一种是抑制Na+-K+-ATPase，另一种是松弛血管。 前列腺素和其他AA氧化作用的观察 代谢物可能作为转运过程的中介(S)，而 角膜上皮与TALH在离子方面的相似性 传输机制，使我们调查了 角膜中存在依赖细胞色素P450的AA代谢 上皮组织。 我们的初步结果首次表明， 角膜上皮含有一种细胞色素P450 能够将AA代谢成几种化合物。到底是什么 这些化合物以及它们是否对 细胞功能和离子运输是将是 在这项研究中提到的。我们预计，基于对 肾脏之语，我们的工作将揭示物质 它们影响Na+-K+-ATPase活性和血管反应性。 事实上，在最近的一次实验中，我们展示了一种 大鼠角膜AA代谢产物对Na~+-K~+-ATPase的抑制作用 眼角膜。Na~+-K~+-ATPase的内源性抑制物 在角膜中合成的物质可能在 依赖这种泵机制的眼部运输上皮细胞。 这些包括角膜上皮和内皮， 睫状体上皮、晶状体包膜下上皮和 视网膜色素上皮。此外，身份识别 一种促进血管扩张的内源性物质可能 在生理学和生物科学的各个领域都有重要意义 病理生理学，如炎症机制，控制 眼循环和房水动力学。

The epithelial cell layers of the cornea can be characterized as a "tight" ion transporting functional syncytium which serves both as a protective barrier to the ocular surface, and as an adjunct fluid- secreting layer assisting the corneal endothelium in the regulation of stromal hydration and, thereby, contributing to the maintenance of corneal transparency. Transport properties of the corneal epithelium are similar to those of the epithelial cells of the thick ascending limb of Henle's loop (TALH), the nephron segment that is important for establishing the solute gradient for urinary concentration through sodium chloride coupled transport. Both transport epithelia possess active chloride transport coupled to Na+-K+-activated ATPase. Recently, we reported that cells of the TALH metabolized arachidonic acid (AA) by cytochrome P450-dependent enzyme(s) to two biologically active metabolites: one inhibits Na+-K+-ATPase and the other relaxes blood vessels. The observations that prostaglandins and other AA oxygenated metabolites may act as a mediator(s) of transport process, and the similarity of the corneal epithelium to TALH as regards ion transport mechanism, led us to investigate the possibility that the cytochrome P450-dependent AA metabolism exists in the corneal epithelium. Our preliminary results demonstrate for the first time that the epithelium of the cornea contains a cytochrome P450 species capable of metabolizing AA to several compounds. Exactly what these compounds are and whether they have biological effects on cell function and ion transport are questions which will be addressed in this study. We expect, based on parallel studies in the TALH of the kidney, that our work will reveal substances which affect Na+-K+-ATPase activity and vascular reactivity. Indeed, in a recent experiment we demonstrated the ability of one of the corneal AA metabolites to inhibit Na+-K+-ATPase of the cornea. Such an endogenous inhibitor of Na+-K+-ATPase synthesized in the cornea may have fundamental importance in ocular transport epithelia that rely on this pump mechanism. These include the corneal epithelium and endothelium, the epithelia of the ciliary body, the lens subcapsular epithelium and the retinal pigment epithelium. Furthermore, the identification of an endogenous substance which promotes vasodilatation may have significance in diverse areas of physiology and pathophysiology such as inflammatory mechanisms, control of the ocular circulation and aqueous humor dynamics.