Lithium induces microcysts and polyuria in adolescent rat kidney independent of cyclooxygenase‐2
Prostanoids derived from endogenous cylooxygenase (COX)-mediated arachidonic acid metabolism play important roles in the maintenance of renal blood flow and salt and water homeostasis. The relative importance of COX-1 and COX-2 isoforms is under active investigation. We have performed a comprehensive histochemical analysis by comparing rat and mouse kidneys for cellular and subcellular localization of COX-1 and -2 and microsomal-type PGE synthase (PGES), the rate-limiting biosynthetic enzyme in PGE2 synthesis. A choice of different sera was compared, and the results were confirmed by antigen-retrieval techniques, in situ hybridization, RT-PCR, and the use of COX knockout mice. In the glomerulus, significant COX-1 expression was detected in a subset of mesangial cells. Along the renal tubule, the known COX-2 expression in cTAL and macula densa was paralleled by PGES staining. In the terminal distal convoluted tubule, connecting tubule, and cortical and medullary collecting ducts, a significant COX-1 signal was colocalized with PGES; COX-2 was not found in these sites. Intercalated cells were generally negative. Cortical fibroblasts were COX-1 and PGES positive in mice, whereas in rats only PGES could be reliably detected. Lipid-laden interstitial cells of the inner medulla were COX-1, -2, and PGES positive. Vascular smooth muscle cells were not stained. The present data support prominent functions of renal prostanoids, predominantly PGE2, by defining expression sites of the key enzymes for their biosynthesis in the rat and mouse. Results define the renal cell types involved in prostaglandin autacoid functions within spatially restricted sites such as the juxtaglomerular apparatus, mesangium, distal convolutions and collecting duct, and in compartments of the renal interstitium.