Involvement of Prostaglandin E2 in Clearance of Aggregated Protein via Protein Kinase A in Glomeruli

The Japanese Journal of Pharmacology

Masayuki Sugiura²  Tsutomu Nishiyama²  Yoshio Suzuki¹  Tadashi Nagamatsu¹  Jun-ichi Koseki¹  Toshiyuki Nagao¹ 

[1] Department of Pharmacology, Faculty of Pharmacy, Meijo University;Toxicology Laboratory, Taisho Pharmaceutical Co., Ltd.

关键词: Glomeruli;    Prostaglandin E2;    Aggregated protein;    Cyclic AMP;    Protein kinase A;   

DOI  :  10.1254/jjp.85.139

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(32)Cited-By(7)Recently we immunohistochemically demonstrated that prostaglandin E2 (PGE2) promoted the clearance of aggregated bovine serum albumin (a-BSA) deposited in glomeruli. Herein, we investigated the role of PGE2 and its signal transduction in the disposal of macromolecules in glomeruli. EP2 and EP4 receptor mRNA was detected in glomeruli by RT-PCR analysis. A-BSA was injected twice into mice. Glomeruli were then isolated and incubated. A-BSA gradually disappeared from isolated glomeruli. PGE2 increased the intracellular cyclic AMP and decreased a-BSA level in glomeruli. Additionally, 8-bromo-cyclic AMP evoked a loss of a-BSA in isolated glomeruli. The effect of 8-bromo-cyclic AMP on the clearance of a-BSA was abolished by KT 5720 in glomeruli. PGE2 and 8-bromo-cyclic AMP also prompted disposal of a-BSA in cultured mesangial cells. These findings indicate that PGE2 positively regulates the removal of macromolecules via cyclic AMP and protein kinase A in glomeruli, and they provide insight into how to prevent the development of glomerulonephritis and glomerulosclerosis.

【 授权许可】

Unknown