Modulation of Anti-Glomerular Basement Membrane Nephritis in Rats by ONO-1301, a Non-Prostanoid Prostaglandin I_2 Mimetic Compound with Inhibitory Activity against Thromboxane A_2 Synthase

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Abstract

The antinephritic effects of ONO-1301 ([7, 8-dihydro-5-[(<I>E</I>)-[[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.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 73(1), 73-82, 1997-01-01

    The Japanese Pharmacological Society

References:  36

Codes

  • NII Article ID (NAID)
    10008676921
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4131797
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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