The role of prostaglandin EP receptors in a model of glomerulonephritis

Abstract

Prostaglandin E2 (PGE2) interacts with four E-Prostanoid (EP) receptor subtypes---designated EP1--4 . In glomerulonephritis (GN), a renal inflammatory disease, inhibition of enhanced renal PGE2 synthesis by nonsteroidal-anti-inflammatory drugs (NSAIDs), results in both beneficial anti-proteinuric effects and deleterious side effects on renal blood flow (RBF) and Na+ homeostasis, implying that one or more EP subtypes may mediate these actions. We set out to investigate the role of the EP1 receptor in GN since it localizes to the collecting duct, where it may regulate Na+ homeostasis, in podocytes and mesangial cells, where it could alter the permeability of the glomerulus, and in arterioles, where EP, receptors may induce vasoconstriction thereby reducing RBF. A mouse model of GN was induced in wildtype (wt) and EP1-/- mice using an anti-rat-glomerular basement membrane (anti-GBM) antibody. Proteinuria was similar in GN wt and GN EP1-/- groups thereby negating a role for this subtype in modulating filtration barrier permeability. (Abstract shortened by UMI.)