A New Endogenous Natriuretic Factor: LLU-α

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 12; pp. 6002 - 6007
• Main Authors: Wechter, William J., Kantoci, Darko, Murray, E. David, D'Amico, Derin C., Jung, Michael E., Wang, Wen-Hui
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 11.06.1996; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Bioassay; Biochemistry; Blood Pressure - drug effects; Cattle; Cells, Cultured; Chromatography; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Diuresis - drug effects; Excretion; Extracellular fluid; Female; Glomerular filtration rate; Hormones; Humans; Hypertension; Kidney - cytology; Kidney - drug effects; Kidney - enzymology; Male; Natriuresis - drug effects; Natriuretic Agents - isolation & purification; Natriuretic Agents - metabolism; Natriuretic Agents - pharmacology; Potassium - urine; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase - drug effects; Ungulates; Urine; Urology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.12.6002

For over three decades, renal physiology has sought a putative natriuretic hormone (third factor) that might control the body's pool of extracellular fluid, an important determinant in hypertension, congestive heart failure, and cirrhosis. In our search for this hormone, we have isolated several pure natriuretic factors from human uremic urine that would appear, alone or in combination, to mark a cluster of phenomena previously presumed to be that of a single ``natriuretic hormone.'' This paper reports the purification, chemical structure, and total synthesis of the first of these compounds, LLU-α , which proved to be 2,7,8-trimethyl-2-(β -carboxyethyl)-6-hydroxychroman, presumably a metabolite of γ -tocopherol. Both natural LLU-α and synthetic material are identical (except for optical activity) with respect to structure and biological activity. It appears that the natriuretic activity of LLU-α is mediated by inhibition of the 70 pS K+ channel in the apical membrane of the thick ascending limb of the kidney.