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Edited* by Gerhard Giebisch, Yale University School of Medicine, New Haven, CT, and approved January 4, 2013 (received for review October 2, 2012)
Abstract
Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: jpluznick{at}jhmi.edu.
Author contributions: J.L.P., J.P.-P., and M.J.C. designed research; J.L.P., R.J.P., H.G., Z.P., A.S., J.H., I.B., L.-X.W., F.R., T.W., and J.P.-P. performed research; M.Y. and J.I.G. contributed new reagents/analytic tools; J.L.P., R.J.P., H.G., Z.P., A.S., I.B., F.R., S.J.F., J.I.G., A.E., and M.J.C. analyzed data; and J.L.P. and M.J.C. wrote the paper.
The authors declare no conflict of interest.
↵*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1215927110/-/DCSupplemental.
SCFA-sensing olfactory GPCR induces renin release
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