Role of serotonin in nephrotoxic serum nephritis in WKY rats.
Our objective was to determine whether serotonin is involved in inducing nephrotoxic serum nephritis in WKY rats. After injection of antiglomerular basement membrane antiserum, urinary protein excretion was significantly decreased in rats treated with the serotonin receptor antagonist, MCI-9042, and in rats treated with p-chlorophenylalanine. Similarly, severe necrotizing lesions and crescent formation were inhibited in a dose-dependent manner by treatment with MCI-9042 and p-chlorophenylalanine. The number of intraglomerular ED-1-positive cells was increased on day 3 and thereafter in the placebo group. A significant increase in the number of crescent lesions was observed in the placebo group on day 7 and thereafter. Neither adenosine diphosphate- nor collagen-induced platelet aggregations were inhibited in platelet-rich plasma from rats treated with MCI-9042. No significant differences were observed in the production of circulating antibody and antibody deposition in rat glomeruli among the study groups. These results indicate that pathologic changes and urinary protein excretion are closely related to the presence of serotonin in nephrotoxic serum nephritis of WKY rats. Thus serotonin may play a key role in the glomerular injury in this model. Studies on the mode of action of MCI-9042 on platelet aggregation in vivo indicate that the antiplatelet effect of this drug did not contribute to the inhibition of renal injury in this experimental model. This study suggests that serotonin participates in macrophage-mediated immune injury in nephrotoxic serum nephritis of WKY rats.
Kanai
H
H
Third Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Hiromura
K
K
Kuroiwa
T
T
Maezawa
A
A
Yano
S
S
Naruse
T
T
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001323:Autoantibodies; D003176:Complement C3 / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010974:Platelet Aggregation / Q000187:drug effects; D011507:Proteinuria / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology
D000906:Antibodies; D001323:Autoantibodies; D003176:Complement C3; D007074:Immunoglobulin G; D012702:Serotonin Antagonists; D013386:Succinates; C051951:antiglomerular basement membrane antibody; C064294:sarpogrelate; D012701:Serotonin; D003404:Creatinine; D010134:Fenclonine