[A study of PGE2-induced signal transduction in aminonucleoside nephrosis]

It has been shown that the renal prostaglandin E2 (PGE2) receptors may be damaged in the experimental nephrosis. Stimulation of PGE2 receptors could result in adenosine 3',5'-cyclic monophosphate (cAMP) accumulation and phosphoinositide (PI) breakdown. In this study, to clarify the mechanism of urinary protein excretion in experimental nephrosis, cAMP accumulation and PI breakdown by PGE2 were investigated in isolated glomeruli and medulla from normal and puromycin aminonucleoside (AN)-induced nephrotic rat kidney at the several stages of experimental nephrosis. Nephrotic rats were prepared by administration of AN (5 mg/100 g b.w.) to Male Wistar rats (200-250 g) intraperitoneally. The kidneys were obtained from the rats one, three or five weeks after the AN administration. The cortex and medulla were minced after perfusion, then isolated glomeruli was obtained from cortex by sieving methods. Cyclic AMP was measured by radioimmunoassay and PI breakdown was monitored by measuring [3H] inositol phosphates (IPs). The results were as follows: 1) Cyclic AMP accumulation stimulated by PGE2 as well as IPs accumulation on basal level were suppressed in experimental nephrosis. 2) There was the difference between the isolated glomeruli and medulla in the recovery time of IPs accumulation on basal level in experimental nephrosis. 3) The response of PI breakdown to PGE2 in experimental nephrosis had been accelerated more than that of control. 4) The PGE2-induced PI breakdown was suppressed by dibutyryl cAMP (dbcAMP).(ABSTRACT TRUNCATED AT 250 WORDS)