Functional expression of the olfactory signaling system in the kidney

Pluznick, Jennifer L.; Zou, Da; Zhang, Xiaohong; Yan, Qingshang; Rodriguez‐Gil, Diego J.; Eisner, Christoph; Wells, Erika; Greer, Charles A.; Wang, Tong; Firestein, Stuart; Schnermann, Jürgen; Caplan, Michael J.

doi:10.1073/pnas.0812859106

Cited by 203 publications

(226 citation statements)

References 37 publications

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“…ORs also play important roles outside of the OE, serving as specialized chemosensors in a variety of tissues (2,3). We have recently demonstrated that major components of the olfactory signaling pathway are present in the kidney, where they play important functional roles in the regulation of both glomerular filtration rate (GFR) and renin release (4). In addition to the olfactory G protein G olf and the olfactory adenylate cyclase AC3, we reported that at least six members of the OR gene superfamily are expressed in renal tissue.…”

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confidence: 99%

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

Pluznick

Protzko

Gevorgyan

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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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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confidence: 99%

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

Pluznick

Protzko

Gevorgyan

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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980

966

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“…Furthermore, ORs maintain up to 40% genetic similarity with rhodopsin (43). Additionally, ORs appear within areas of mammalian corpus that have no olfactory capacity (44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). We therefore hypothesize that due to functional and morphological similarities, if ORs are activated through an ET mechanism, other GPCRs share the same fundamental mechanism.…”

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confidence: 99%

Experimental evaluation of the generalized vibrational theory of G protein-coupled receptor activation

Hoehn

Nichols

McCorvy

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Recently, an alternative theory concerning the method by which olfactory proteins are activated has garnered attention. This theory proposes that the activation of olfactory G protein-coupled receptors occurs by an inelastic electron tunneling mechanism that is mediated through the presence of an agonist with an appropriate vibrational state to accept the inelastic portion of the tunneling electron's energy. In a recent series of papers, some suggestive theoretical evidence has been offered that this theory may be applied to nonolfactory G protein- O lfaction-and other chemo-sensitive sensory processes-is an important information-gathering technique for organisms of many clades and kingdoms. Specifically, human olfaction is known to occur by activation of olfactory receptors (ORs)-a subclass of G protein-coupled receptors (GPCRs)-located within the nasal epithelium and mediating responses within the olfactory bulb, where it is encoded and conveys information to the amygdala, the orbitofrontal cortex, and the hippocampus (1, 2). The discovery and the cloning of ORs led to the joint 2004 Nobel Prize in Physiology and Medicine to Richard Axel and Linda Buck. (3) GPCRs are 7-helical transmembrane proteins, facilitating communication from extracellular ligand signals to the cellular interior through activation of (interior) G proteins, while maintaining the integrity of the membrane (4). GPCRs are activated by an appropriate agonist moving into the protein's orthosteric binding site, resulting in a conformational change within the helical bundle. This structural change leads to altered conformations of the intracellular loops that couple to appropriate signaling molecules within the cell, e.g., G proteins. A recent series of papers has experimentally determined activated/inactivated states through isotopic-tagged receptors with NMR spectroscopy (5-7). An additional work used molecular dynamics to provide structural insights into how the agonist may assist the interchange between conformations through several proposed peptide sidechain pathways by examining the structures of the activated and inactivated µ-opioid receptor (8). Additionally, photon-induced conformational changes in lightsensitive proteins have also been observed (9, 10).Recently, an iteration of the vibrational theory of olfaction (VTO)-suggested and advocated by Luca Turin (11, 12)-has arisen and has gained both supporters (13-16) and detractors (17, 18); the novelty of this incarnation of the VTO is ascribable to its nonthermal-and nonphoton-based mechanism. Turin's theory is a contemporary reincarnation of the more classical theory proposed by Dyson (19), Wright (20), and Wright and Serenius (21), where the activation of the olfactory receptor is performed-or sensitive to-the molecular vibrations of the olfactant. Dyson suggested that the molecular vibrations of the agonist were exactly responsible for the activation of the protein. These vibrations were entirely thermally excited, as no mechanism for photoexcitation is available within the body. Th...

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“…One of the novel renal G‐protein‐coupled receptors we are interested in is olfactory receptor 78 (Olfr78; Pluznick et al . 2009). Although our original intention was to study the role of Olfr78 in whole‐animal physiology, through the course of these studies we came to realize that the functional role of Olfr78 is intimately tied together with short‐chain fatty acid (SCFA) metabolites produced by the gut microbiota by breaking down complex dietary polysaccharides (Pluznick et al .…”

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confidence: 99%

Olfaction in the kidney: ‘smelling’ gut microbial metabolites

Natarajan

Pluznick

2015

Experimental Physiology

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New Findings What is the topic of this review? This review covers recent findings highlighting roles for renal and vascular sensory receptors that modify blood pressure control in response to changes in gut microbial metabolites. What advances does it highlight? This review highlights the novel roles that G‐protein‐coupled receptor 41 and olfactory receptor 78 play in blood pressure regulation. The gut microbiota have recently been recognized as an important component of host physiology and pathophysiology. Our recent studies have shown that a subset of gut microbial metabolites, known as short‐chain fatty acids, act as ligands for host G‐protein‐coupled receptors (G‐protein‐coupled receptor 41 and olfactory receptor 78). Short‐chain fatty acid‐mediated activation of G‐protein‐coupled receptor 41 and olfactory receptor 78 modulates blood pressure control, both by modulating renin secretion and by modulating vascular tone directly. Further studies are needed in order to gain a better understanding of the underlying mechanism by which microbiota and microbial metabolites modulate host physiology and their potential implications in health and disease.

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Functional expression of the olfactory signaling system in the kidney

Cited by 203 publications

References 37 publications

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

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

Experimental evaluation of the generalized vibrational theory of G protein-coupled receptor activation

Olfaction in the kidney: ‘smelling’ gut microbial metabolites

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