The sense of smell in mammals allows specific detection of a huge array of chemicals in our environment. The detection is accomplished by a large array of over 1000 olfactory receptors. These related receptors are all coupled by heterotrimeric guanine nucleotide–binding protein (G protein) to a particular isoform of adenylate cyclase, AC3. Pluznick et al. wondered whether this elaborate system might also be implemented for other purposes—in particular sensing of the chemical composition of the extracellular body fluids that are filtered through the kidneys. They detected mRNAs encoding the olfactory G protein Golf and AC3 in the mouse kidney and confirmed presence of the proteins by immunoblotting. Immunohistochemistry showed AC3 and Golf to be localized to the cells of the macula densa, which control glomerular filtration rate in part by secretion of the enzyme renin. In knockout animals lacking AC3, the glomerular filtration rate was decreased and amounts of renin in the blood were decreased, presumably because of reduced secretion by the kidneys. The ligands for the six olfactory receptors found in the kidney are not known, but the authors suggest that it would make sense for the kidney to respond to the presence of various chemicals such as metabolites; xenobiotics, which need to be cleared from the system; or dicarboxylic acids, which can lead to the formation of kidney stones.
J. L. Pluznick, D.-J. Zou, X. Zhang, Q. Yan, D. J. Rodriguez-Gil, C. Eisner, E. Wells, C. A. Greer, T. Wang, S. Firestein, J. Schnermann, M. J. Caplan, Functional expression of the olfactory signaling system in the kidney. Proc. Natl. Acad. Sci. U.S.A. 106, 2059–2064 (2009). [Abstract] [Full Text]