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Identification of a Forskolin-Like Molecule in Human Renal Cysts

William C. Putnam^*, Sarah M. Swenson^*, Gail A. Reif, Darren P. Wallace, George M. Helmkamp, Jr. and Jared J. Grantham^,

^* Midwest Research Institute, Kansas City, Missouri; and Kidney Institute and Department of Biochemistry and Molecular Biology, Kansas University Medical Center, Kansas City, Kansas

Address correspondence to: Dr. Jared J. Grantham, The Kidney Institute, Mailstop 3018, Kansas University Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160. Phone: 913-588-7605; Fax: 913-588-9251; E-mail: jgrantha{at}kumc.edu

Received for publication November 8, 2006. Accepted for publication December 7, 2006.

Renal cyst enlargement is increased by adenosine cAMP, which is produced within mural epithelial cells. In a search for modulators of cAMP synthesis cyst fluids from 18 patients with autosomal dominant or recessive polycystic kidney disease (PKD) were analyzed, and in 15 of them, a stable lipophilic molecule that increased cAMP levels, stimulated transepithelial chloride and fluid secretion, and promoted the proliferation of human cyst epithelial cells was characterized. With the use of HPLC-mass spectrometry, a bioactive lipid with the same mass spectral fingerprint, the same chromatographic retention time, and the same biologic properties as forskolin, a widely known, potent adenylyl cyclase agonist, has been isolated and identified within the cyst fluid. Forskolin is synthesized by the plant Coleus forskohlii, but its appearance or compounds like it have not been reported in animals. The origin of forskolin in patients with PKD was not revealed by this study. Synthesis by mural cyst epithelial cells or an exogenous source are the most likely possibilities. Forskolin is sold for weight management and as a cardiovascular tonic in health stores and through the Worldwide Web. It is concluded that forskolin may have a role in promoting the enlargement of cysts in autosomal dominant PKD and recommended that patients avoid oral and parenteral preparations that contain this compound.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673