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PNAS 106 (6): 2059-2064

Copyright © 2009 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / PHYSIOLOGY

Functional expression of the olfactory signaling system in the kidney

Jennifer L. Pluznicka, Dong-Jing Zoub, Xiaohong Zhangb, Qingshang Yana, Diego J. Rodriguez-Gilc, Christoph Eisnerd, Erika Wellsa, Charles A. Greerc, Tong Wanga, Stuart Firesteinb, Jurgen Schnermannd, and Michael J. Caplana,1

aDepartment of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06520; bDepartment of Biological Sciences, Columbia University, New York, NY 10027; cDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06510; and dNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892

Communicated by Edward A. Adelberg, Yale University, New Haven, CT, December 17, 2008

Received for publication November 3, 2008.

Abstract: Olfactory-like chemosensory signaling occurs outside of the olfactory epithelium. We find that major components of olfaction, including olfactory receptors (ORs), olfactory-related adenylate cyclase (AC3) and the olfactory G protein (Golf), are expressed in the kidney. AC3 and Golf colocalize in renal tubules and in macula densa (MD) cells which modulate glomerular filtration rate (GFR). GFR is significantly reduced in AC3–/– mice, suggesting that AC3 participates in GFR regulation. Although tubuloglomerular feedback is normal in these animals, they exhibit significantly reduced plasma renin levels despite up-regulation of COX-2 expression and nNOS activity in the MD. Furthermore, at least one member of the renal repertoire of ORs is expressed in a MD cell line. Thus, key components of olfaction are expressed in the renal distal nephron and may play a sensory role in the MD to modulate both renin secretion and GFR.

Key Words: adenylate cyclase 3 • glomerular filtration rate • Golf • macula densa • renin

Author contributions: J.L.P., J.S., and M.J.C. designed research; J.L.P., Q.Y., D.J. R.-G., C.E., E.W., and J.S. performed research; D.-J.Z., X.Z., Q.Y., D.J.R.-G., C.A.G., T.W., and S.F. contributed new reagents/analytic tools; J.L.P., T.W., S.F., J.S., and M.J.C. analyzed data; and J.L.P., J.S., and M.J.C. wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0812859106/DCSupplemental.

1To whom correspondence should be addressed at: 333 Cedar Street, SHM B-147, Yale University School of Medicine, New Haven, CT 06510. E-mail: michael.caplan{at}yale.edu

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