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-SCKKYCDPWEVIDGSCGLFNSKYCCREK 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 > or = 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 Ca(2+)-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.
Bateman
A
A
Royal Victoria Hospital, Department of Medicine, McGill University, Montreal, Quebec, Canada.
MacLeod
R J
RJ
Lembessis
P
P
Hu
J
J
Esch
F
F
Solomon
S
S
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D023082:Defensins; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D007668:Kidney / Q000737:chemistry*; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000305:Adrenal Cortex Hormones; D001798:Blood Proteins; D023082:Defensins; D011506:Proteins; C099428:RK-1 protein, Oryctolagus cuniculus; D000324:Adrenocorticotropic Hormone; D012964:Sodium