Thromboxane A2 Interferes with a Disposal Process of Aggregated Protein in Glomeruli.
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概要
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Immune complexes in glomeruli are involved in development of diverse glomerulonephritis. The disposal process of glomerular immune complexes has been unclarified. The present studies were undertaken to determine if thromboxane A<SUB>2</SUB> (TXA<SUB>2</SUB>) is associated with the disposal of macromolecules in the glomeruli using mice injected with aggregated bovine serum albumin (a-BSA). A-BSA promptly accumulated in the glomeruli, the level reaching a plateau at 6 hr after the injection of a-BSA, and then decreased by 48 hr. The production of glomerular TXA<SUB>2</SUB>, prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) and prostaglandin I<SUB>2</SUB> concomitantly increased with the decrease of a-BSA in the glomeruli. TXA<SUB>2</SUB> synthase inhibitors and TXA<SUB>2</SUB> receptor antagonists accelerated clearance of glomerular a-BSA without enhancing renal tissue blood flow. They did not affect a-BSA level in the plasma. In contrast, aminophylline, dopamine and mannitol significantly increased renal tissue blood flow, but did not decrease glomerular a-BSA. TXA<SUB>2</SUB> synthase inhibitors decreased TXA2 production in the glomeruli. TXA<SUB>2</SUB> synthase inhibitors and TXA<SUB>2</SUB> receptor antagonists did not influence the generation of PGE<SUB>2</SUB>. The TXA<SUB>2</SUB> analogue U-46619 significantly increased the accumulation of a-BSA in the glomeruli. We propose that TXA<SUB>2</SUB> interferes with the disposal process of aggregated protein in the glomeruli. We also postulate that interception of glomerular activity of TXA<SUB>2</SUB> may be an effective intervention for managing immune complex-mediated glomerulonephritis and glomerulosclerosis.
- 公益社団法人 日本薬理学会の論文
著者
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Nagamatsu Tadashi
Department Of Pharmacobiology And Therapeutics Faculty Of Pharmacy Meijo University
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Nagao Toshiyuki
Department Of Pharmacology Faculty Of Pharmacy Meijo University
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Nomura Yosuke
Department Of Pharmacology Faculty Of Pharmacy Meijo University
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Suzuki Yoshio
Department Of Chemical Science & Technology Faculty Of Engineering Kyushu University
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