title: COX-2 inhibition and prostaglandin receptors in experimental nephritis.
abstract: BACKGROUND
  Renal cyclooxygenases (COX) produce the prostaglandins (PG) E2, I2 and thromboxane (TxA2), which interact with distinct G protein-coupled receptors. We investigated the expression of the three EP receptors EP2, EP3 and EP4 and the receptors for PGI2 (IP) and TxA2 (TP) in rats with passive Heymann nephritis (PHN). We studied their regulation by COX-2 inhibition with celecoxib.
  
  
  METHODS
  Four groups of Wistar rats were studied: healthy rats (group A), healthy rats treated with celecoxib (group B), rats with PHN (group C), and rats with PHN receiving celecoxib (group D). Expression of the mRNA for all receptors in the renal cortex and for the EP3 receptor in cultured mesangial cells (MCs) was determined by semiquantitative reverse transcriptase polymerase chain reaction. Stable prostaglandin metabolites were measured in the urine by radioimmunoassay.
  
  
  RESULTS
  Rats with PHN (group C) showed an 1.8-fold increase of cortical EP3 receptor mRNA expression as compared with controls (group A). In celecoxib-treated PHN rats (group D) the mRNA expression of the EP3 and EP4 receptors was significantly reduced to 1.0-fold and 0.7-fold induction, respectively. Furthermore, the excretion of bicyclo-prostaglandin E2 (PGE2) was inhibited by celecoxib. No changes were observed in the expression of the other PG-receptors. In cultured MC, PGE2 enhanced the EP3 mRNA expression.
  
  
  CONCLUSIONS
  These data suggest a predominant role of the EP3 receptor in the transduction of PGE2-actions in PHN. It was concluded that COX-2-dependent PGE2 is able to potentiate its effects in the kidney by up-regulating its own receptors.
authors.affiliation: Heinrich Heine Universität Düsseldorf, Düsseldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Waldner
authors.forename: G
authors.initials: G
authors.lastname: Heise
authors.forename: K
authors.initials: K
authors.lastname: Schrör
authors.forename: P
authors.initials: P
authors.lastname: Heering
mesh_terms: D000818:Animals; D000068579:Celecoxib; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology / Q000652:urine; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000378:metabolism; D005921:Glomerulonephritis / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011720:Pyrazoles; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D015232:Dinoprostone