RGD Reference Report - COX-2 inhibition and prostaglandin receptors in experimental nephritis. - Rat Genome Database

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COX-2 inhibition and prostaglandin receptors in experimental nephritis.

Authors: Waldner, C  Heise, G  Schror, K  Heering, P 
Citation: Waldner C, etal., Eur J Clin Invest. 2003 Nov;33(11):969-75.
RGD ID: 10043359
Pubmed: PMID:14636300   (View Abstract at PubMed)

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. 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 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGER3Humanmembranous glomerulonephritis  ISOPtger3 (Rattus norvegicus)mRNA:increased expression:renal cortex (rat)RGD 
Ptger3Ratmembranous glomerulonephritis  IEP mRNA:increased expression:renal cortex (rat)RGD 
Ptger3Mousemembranous glomerulonephritis  ISOPtger3 (Rattus norvegicus)mRNA:increased expression:renal cortex (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ptger3Ratcellular response to lipopolysaccharide  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptger3  (prostaglandin E receptor 3)

Genes (Mus musculus)
Ptger3  (prostaglandin E receptor 3 (subtype EP3))

Genes (Homo sapiens)
PTGER3  (prostaglandin E receptor 3)


Additional Information