Olfactory receptor responding to gut microbiotaderived signals plays a role in renin secretion and blood pressure regulation

Jennifer L. Pluznick, Ryan J. Protzko, Haykanush Gevorgyan, Zita Peterlin, Arnold Sipos, Jinah Han, Isabelle Brunet, La Xiang Wan, Federico Rey, Tong Wang, Stuart J. Firestein, Masashi Yanagisawa, Jeffrey I. Gordon, Anne Eichmann, Janos Peti-Peterdi, Michael J. Caplan

Research output: Contribution to journalArticle

404 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4410-4415
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number11
DOIs
StatePublished - Mar 12 2013

Keywords

  • GPCR
  • MOL2.3
  • MOR18-2
  • OR51E2

ASJC Scopus subject areas

  • General

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    Pluznick, J. L., Protzko, R. J., Gevorgyan, H., Peterlin, Z., Sipos, A., Han, J., Brunet, I., Wan, L. X., Rey, F., Wang, T., Firestein, S. J., Yanagisawa, M., Gordon, J. I., Eichmann, A., Peti-Peterdi, J., & Caplan, M. J. (2013). Olfactory receptor responding to gut microbiotaderived signals plays a role in renin secretion and blood pressure regulation. Proceedings of the National Academy of Sciences of the United States of America, 110(11), 4410-4415. https://doi.org/10.1073/pnas.1215927110