Jpn. J. Pharmacol. 85 (2), 139-145 (2001)

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

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

1Department of Pharmacology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan
2Toxicology Laboratory, Taisho Pharmaceutical Co., Ltd., Yoshinocho, Omiya 330-0031, Japan
*Corresponding author. FAX: +81-52-834-8780

Abstract: 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.

Keywords: Glomeruli, Prostaglandin E2, Aggregated protein, Cyclic AMP, Protein kinase A

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