Статья

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

Jennifer L. PluznickDepartment of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;Ryan J. ProtzkoDepartment of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;Haykanush GevorgyanDepartments of Physiology and Biophysics and Medicine, University of Southern California, Los Angeles, CA 90033;Zita PeterlinDepartment of Biological Sciences, Columbia University, New York, NY 10027;Arnold SiposDepartments of Physiology and Biophysics and Medicine, University of Southern California, Los Angeles, CA 90033;Jinah HanDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;Isabelle BrunetCenter for Interdisciplinary Research in Biology, College de France, 75231 Paris, France;La-Xiang WanDepartment of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520;Federico E. ReyTong WangDepartment of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520;Stuart FiresteinDepartment of Biological Sciences, Columbia University, New York, NY 10027;Masashi YanagisawaDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390Jeffrey I. GordonAnne EichmannDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;János Peti‐PeterdiDepartments of Physiology and Biophysics and Medicine, University of Southern California, Los Angeles, CA 90033;Michael J. CaplanDepartment of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520;

2013en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1073/pnas.1215927110

Цитирования и источники

Цитирований: 2Использованных источников: 0

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