Renal epithelial fluid secretion and cyst growth: the role of cyclic AMP.
Transepithelial fluid secretion has been postulated to account for the accumulation of fluid within hereditary and acquired renal cysts, but no such mechanism has been demonstrated in human kidney epithelium. It is shown here that transepithelial fluid secretion was stimulated by prostaglandin E1 (PGE1), forskolin, 8-Br-cyclic AMP, and 1-methyl-3-isobutylxanthine in polarized monolayers of established renal cell lines (MDCK and rat glomerular epithelial cells) and in monolayer cultures derived from the cyst walls of human autosomal dominant polycystic kidney disease and from epithelial cells of normal human renal cortex. Treatment with cyclic AMP agonists caused the same cells, when dispersed within a gel matrix of type I collagen (Vitrogen), to proliferate and form spherical fluid-filled monolayered cysts. Our findings suggest that increased intracellular cyclic AMP levels may have a critical role in the formation and expansion of hereditary and acquired renal cysts.
Mangoo-Karim
R
R
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Uchic
M E
ME
Grant
M
M
Shumate
W A
WA
Calvet
J P
JP
Park
C H
CH
Grantham
J J
JJ
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004285:Dogs; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D052177:Kidney Diseases, Cystic / Q000473:pathology / Q000503:physiopathology*; D051381:Rats
D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D000527:Alprostadil; D015056:1-Methyl-3-isobutylxanthine