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COX‐2 inhibition and prostaglandin receptors in experimental nephritis
Author(s) -
Waldner C.,
Heise G.,
Schrör K.,
Heering P.
Publication year - 2003
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2003.01256.x
Subject(s) - prostaglandin e2 receptor , receptor , prostaglandin e2 , medicine , endocrinology , prostaglandin e , prostaglandin , thromboxane a2 , chemistry , thromboxane , biology , platelet , agonist
Abstract Background Renal cyclooxygenases (COX) produce the prostaglandins (PG) E 2 , I 2 and thromboxane (TxA 2 ), which interact with distinct G protein‐coupled receptors. We investigated the expression of the three EP receptors EP 2 , EP 3 and EP 4 and the receptors for PGI 2 (IP) and TxA 2 (TP) in rats with passive Heymann nephritis (PHN). We studied their regulation by COX‐2 inhibition with celecoxib. Materials and 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 EP 3 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 EP 3 receptor mRNA expression as compared with controls (group A). In celecoxib‐treated PHN rats (group D) the mRNA expression of the EP 3 and EP 4 receptors was significantly reduced to 1·0‐fold and 0·7‐fold induction, respectively. Furthermore, the excretion of bicyclo‐prostaglandin E 2 (PGE 2 ) was inhibited by celecoxib. No changes were observed in the expression of the other PG‐receptors. In cultured MC, PGE 2 enhanced the EP 3 mRNA expression. Conclusions These data suggest a predominant role of the EP 3 receptor in the transduction of PGE 2 ‐actions in PHN. It was concluded that COX‐2‐dependent PGE 2 is able to potentiate its effects in the kidney by up‐regulating its own receptors.