Protective effect of prostaglandin EP4-receptor agonist on anti-glomerular basement membrane antibody-associated nephritis.
Prostaglandin E(2)-receptor subtypes, EP(1), EP(2), EP(3), and EP(4), are present in the kidney. The aim of this study was to elucidate the anti-nephritic effect of an EP(4)-receptor agonist on an experimental nephritic model. Mice were injected i.v. with anti-glomerulus antiserum to induce nephritis. Nephritic glomeruli generated more prostaglandin E(2) (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 EP(4) agonist, at 10(-5) M. Nephritic glomeruli expressed a lesser amount of mRNA of prostaglandin E(2)-receptor subtypes as compared with normal glomeruli. AE1-329 was administered s.c. at 100 microg/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 EP(4)-receptor agonists are a promising drug to prevent the development of glomerulonephritis.
Nagamatsu
Tadashi
T
Laboratory of Pharmacobiology and Theraperutics, Faculty of Pharmaceutical Science, Meijo University, Japan. nagamats@ccmfs.meijo-u.ac.jp
Imai
Hirohito
H
Yokoi
Michiyo
M
Nishiyama
Tsutomu
T
Hirasawa
Yasushi
Y
Nagao
Toshiyuki
T
Suzuki
Yoshio
Y
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001323:Autoantibodies; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007106:Immune Sera; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D058309:Receptors, Prostaglandin E, EP4 Subtype
D000906:Antibodies; D001323:Autoantibodies; D007106:Immune Sera; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; C051951:antiglomerular basement membrane antibody; D000242:Cyclic AMP