Gene expression of prostanoid forming enzymes along the rat nephron.

To obtain information about the general capability of nephron segments to elaborate prostanoids, we determined the gene expression of key enzymes for prostanoid formation.

For this goal mRNAs were assayed for cyclooxygenases-1 and -2 as well as for the synthases of prostaglandin D₂ (PGD₂), prostaglandin E₂ (PGE₂), prostacyclin (PGI₂) and thromboxane A₂ (TXA₂) in microdissected rat nephron segments by RT-PCR.

Cyclooxygenase-1 (COX-1) mRNA was strongly expressed in all segments of the collecting ducts and to a lesser extent in glomeruli. COX-2 mRNA was found in the cortical thick ascending limb of Henle, and weaker expression also was detected in glomeruli. The lipocalin-type PGD synthase mRNA displayed a broad expression pattern in the cortex and outer medulla, including proximal convoluted tubule, thick ascending limb of Henle, distal convoluted tubule, and cortical and outer medullary collecting duct. The hematopoietic PGD synthase mRNA was restricted to the outer medullary collecting duct, and the membrane-associated PGE-synthase mRNA was exclusively expressed in the whole collecting duct system. Prostacylin-synthase mRNA was found in the whole kidney, but not in any microdissected nephron segment analyzed in this study. TXA-synthase mRNA was expressed in glomeruli.

Given that the existence of cyclooxygenase in combination with the different PG-synthases is a prerequisite for the formation of prostanoids, our data suggest that PGD₂ is mainly formed in the thick ascending limb and in the collecting duct, while PGE₂ appears to be mainly generated by the collecting ducts. Probably no formation of PGI₂ occurs within the nephron. Whether TXA₂ can be formed by nephron segments remains questionable.