Kinetics of Rena1 Dispositon and Pharmacological Effect of Peptides

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Recent discovery of various bioactive peptides prompted their application to the treatment of dlseases, and the kidney is recognized as an important organ to regulate the disposition of peptide drugs. In the present study, we have investigated the renal disposition of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and granulocyte-colony stimulating factor (GCSF) in rats, and kinetically analyzed the pharmacologic effect of peptides.1. The isolated perfusion study of rat kidney has shown that the major elimination route of GCSF in the kidney is the glomerular filtration and the filtrated GCSF could be transferred into the renal tissue from the luminal side by the saturable process.2. The filtration fraction and the renal distribution of asialo-GCSF were greater than those of disialo- and monosialo-GCSF.A GCSF conjugate with poly-(stirene-co-maleic acid) was able to escape from glomerular filtration and showed a higher neutrophil-proliferating activity- after i.v.administration to rats compared to GCSF.3. The population analysis enabled quantification of net diuretic activities of ANP and BNP, and also assessment of the effects of hemodynamic change and an inhibitor of neutral endopeptidase.4. Utilizing LLC-PK_1 cell monolayrs cultured on permeable supports, the presence of natriuretic peptide receptors was indicated in both the apical and basolateral membranes in the kidney epithelial cells.