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
E-mail: nagamats@meijo-u.ac.jp
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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