Modulation of Anti-Glomerular Basement Membrane Nephritis in Rats by ONO-1301, a Non-Prostanoid Prostaglandin I2 Mimetic Compound with Inhibitory Activity against Thromboxane A2 Synthase

The Japanese Journal of Pharmacology

Tatsuya Oka¹  Yoshio Suzuki¹  Kazumi Hayashi¹  Tadashi Nagamatsu¹ 

[1] Department of Pharmacology, Faculty of Pharmacy, Meijo University

关键词: ONO-1301;    Anti-glomerular basement membrane (GBM)nephritis;    Vascular cell adhesion molecule;    cAMP;   

DOI  :  10.1254/jjp.73.73

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(36)Cited-By(13)The antinephritic effects of ONO-1301 ([7, 8-dihydro-5-[(E)-[[a-(3-pyridyl)benzylidene]aminooxy]ethyl] -1-naphtyloxy]acetic acid)on crescentic-type anti-glomerular basement membrane (GBM) nephritis in rats were investigated. ONO-1301 was orally given to crescentic-type anti-GBM nephritic rats for 40 days after the induction of nephritis. ONO-1301 (30 mg/kg) suppressed the elevation of protein excretion into urine. In the ONO-1301-treated rats, cholesterol and urea nitrogen content in the plasma was lower than that of the nephritic control rats. Histological observation demonstrated that ONO-1301 suppressed the incidence of crescent formation and adhesion of capillary wall to Bowman''s capsule. However, ONO-1301 failed to inhibit the antibody production against rabbit IgG and the rat-IgG deposition on the GBM. The increase in very late antigen-4 (CD49b, VLA-4) -positive cells in nephritic glomeruli was significantly reduced by ONO-1301 treatment on day 5. cAMP-elevating agents inhibited the up-regulation of vascular cell adhesion molecule-1 (VCAM-1) expression on the surface of human umbilical vein endothelial cells (HUVECs) mediated by tumor necrosis factor (TNF) -α. These findings suggest that the antinephritic action of ONO-1301 is due to, at least in part, inhibition of intraglomerular accumulation of leukocytes through the prevention of the up-regulation of VCAM-1.

【 授权许可】

Unknown