TY - JOUR
T1 - A new endogenous natriuretic factor
T2 - LLU-α
AU - Wechter, William J.
AU - Kantoci, Darko
AU - Murray, E. David
AU - D'Amico, Derin C.
AU - Jung, Michael E.
AU - Wang, Wen Hui
PY - 1996/6/11
Y1 - 1996/6/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0030013245&partnerID=8YFLogxK
U2 - 10.1073/pnas.93.12.6002
DO - 10.1073/pnas.93.12.6002
M3 - Article
C2 - 8650209
AN - SCOPUS:0030013245
SN - 0027-8424
VL - 93
SP - 6002
EP - 6007
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
ER -