Protective Effect of Prostaglandin EP₄-Receptor Agonist on Anti-glomerular Basement Membrane Antibody-Associated Nephritis

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Prostaglandin E₂-receptor subtypes, EP₁, EP₂, EP₃, and EP₄, are present in the kidney. The aim of this study was to elucidate the anti-nephritic effect of an EP₄-receptor agonist on an experimental nephritic model. Mice were injected i.v. with anti-glomerulus antiserum to induce nephritis. Nephritic glomeruli generated more prostaglandin E₂ (2.6 and 0.7 ng) and less cyclic AMP than normal glomeruli (11 and 26 pmol). The production of cyclic AMP in nephritic glomeruli increased 67% in response to AE1-329, an EP₄ agonist, at 10⁻⁵ M. Nephritic glomeruli expressed a lesser amount of mRNA of prostaglandin E₂-receptor subtypes as compared with normal glomeruli. AE1-329 was administered s.c. at 100 μg/kg per day for 3 weeks. AE1-329 suppressed the increase in creatinine and cholesterol compared to those in the control nephritic mice. AE1-329-treated nephritic mice had less crescentic glomeruli and less deposition of rabbit IgG (anti-glomerular basement membrane antibody) in glomeruli than the control mice. AE1-329 prevented the development of glomerulonephritis. These findings suggest that EP₄-receptor agonists are a promising drug to prevent the development of glomerulonephritis.