The isolation and characterization of a novel corticostatin/defensin-like peptide from the kidney

We report the isolation and characterization of RK-1, a novel peptide found in the kidney. RK-1 is related to the corticostatin/defensins and has the sequence MPC SCKKYCDPWEVIDGSCGLFNSKYICCREK but differs from the very cationic corticostatins/defensins in having only one arginine and a calculated charge at pH 7 of +1. Like some myeloid corticostatin/defensins RK-1 inhibits the growth of Escherichia coli. Since corticostatin/defensins effect ion flux in responsive epithelia we used volume changes in villus enterocytes as a model system to study the effects of RK-1 on ion channels in epithelial cells. At concentrations greater than or equal to 10(-9) M RK-1 decreased enterocyte volume in a dose-dependent manner through a pathway that requires extracellular calcium and is inhibited by niguldipine, a dihydropyridine-sensitive ''L''-type Ca2+-channel blocker. In other assay systems for corticostatin/defensins, such as the inhibition of adrenocorticotropin-stimulated steroidogenesis, or cell lysis, RK-1 was inactive or only weakly active. These results demonstrate the existence of a novel system of biologically active peptides in the kidney represented by RK-1 which is antimicrobial and can activate epithelial ion channels in vitro.