| Research Abstract |
l. Characteristies of nephron heterogeneity supporting screening systems tor the evaluation of renal drug actions.
The results obtained include nephron energy metabolism, localization of purine-metabolizing enzymes, inhibitory effect of CAMP on superoxide generation in gloseruli, biphasic increasing effect of angiotensin I]on cytosolic calcium transient in early proximal tubule, a novel vasopressin receptor in the proximal tubule, localization of glycine avidinotransferase within the kidney, lipid peroxidation in rat nephron segments, and intrarenal handling of proteins in rats.
2. Screening systems for the evaluation of kidney-acting drugs.
Intrarenal sites of PGE2 production are highly heterogeneous, and loop diuretics increase PGE2 accuiu'ation selectively in the thick ascending limb suggesting PGE2 as a possible physiological mediator to cause diuresis. Furosemide also acts on short loop of descending thin limb, but not on Ions loop, that could be concluded by determining ATP turnover
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using isolated nephron seg2ents. Antinephrotic drugs potentiate adenosine action on glo2eruli which is well correlated with 'suppressive effect on free radical formation. Estimation of intranephron lipid peroxidation makes it possible to identify the early proximal tubule as a causative site of early stage in diabetic nephropathy. Frog urinary bladde can be used to identify intra cellular nechanislis of renal drug action especially on sodium ion transport coupled with protein kinase C.
3. Screening systems for the evaluation of nephrotoxicity.
Intracellular ATP turnover and agonist-induced cytosolic free calcium transients are sensitive and useful determinants to quantify nephrotoxicity along the nephron. Metabolic functions such as renal gluconeogenesis and ammoniagenesis can be used to find very early signs of nephrotoxicity prior to histological alterations.
The above-summarized results can not only classify kidney-acting and nephrotoxic drugs, but also bring notable informations for the better understanding nechanisums of these drug actions. Less
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