Unsung renal receptors: orphan G‐protein‐coupled receptors play essential roles in renal development and homeostasis

Rajkumar, Premraj; Pluznick, Jennifer L.

doi:10.1111/apha.12813

Cited by 4 publications

(3 citation statements)

References 114 publications

(218 reference statements)

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“…GPR99, or OXGR1, is an α-ketoglutarate receptor that was originally thought to be a P2Y receptor [31]. This receptor is expressed in the kidney, placenta, trachea, salivary glands, lungs, and smooth muscle cells, as well as in some brain regions; in addition to its effects on acid-base homeostasis, it is also involved in axon growth [32][33][34][35]. GPR99 is considered the third CysLT receptor (CysLTR 3 ) due to its high affinity for LTE 4 .…”

Section: Cysteinyl Leukotrienes-multifunctional Inflammation Mediator...mentioning

confidence: 99%

Leukotrienes vs. Montelukast—Activity, Metabolism, and Toxicity Hints for Repurposing

Marques

Justino

2022

Pharmaceuticals

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Increasing environmental distress is associated with a growing asthma incidence; no treatments are available but montelukast (MTK)—an antagonist of the cysteinyl leukotrienes receptor 1—is widely used in the management of symptoms among adults and children. Recently, new molecular targets have been identified and MTK has been proposed for repurposing in other therapeutic applications, with several ongoing clinical trials. The proposed applications include neuroinflammation control, which could be explored in some neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases (AD and PD). However, this drug has been associated with an increasing number of reported neuropsychiatric adverse drug reactions (ADRs). Besides, and despite being on the market since 1998, MTK metabolism is still poorly understood and the mechanisms underlying neuropsychiatric ADRs remain unknown. We review the role of MTK as a modulator of leukotriene pathways and systematize the current knowledge about MTK metabolism. Known toxic effects of MTK are discussed, and repurposing applications are presented comprehensively, with a focus on AD and PD.

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Section: Cysteinyl Leukotrienes-multifunctional Inflammation Mediator...mentioning

confidence: 99%

Leukotrienes vs. Montelukast—Activity, Metabolism, and Toxicity Hints for Repurposing

Marques

Justino

2022

Pharmaceuticals

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“…There are several publications that outline the response of OXGR1 to ligands other than LTE 4 (see review Rajkumar and Pluznick 2017). However, such findings are beyond the scope of this review and will not be discussed further here.…”

Section: Leukotriene Receptorsmentioning

confidence: 99%

A review of non-prostanoid, eicosanoid receptors: expression, characterization, regulation, and mechanism of action

Biringer

2021

J. Cell Commun. Signal.

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Eicosanoid signaling controls a wide range of biological processes from blood pressure homeostasis to inflammation and resolution thereof to the perception of pain and to cell survival itself. Disruption of normal eicosanoid signaling is implicated in numerous disease states. Eicosanoid signaling is facilitated by G-protein-coupled, eicosanoid-specific receptors and the array of associated G-proteins. This review focuses on the expression, characterization, regulation, and mechanism of action of non-prostanoid, eicosanoid receptors.

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“…A number of G‐protein‐coupled “orphan” receptors with no known ligand have been identified in both olfactory epithelium and the kidney (for review see ref. ) and some of them contribute to the regulation of kidney function and blood pressure . In the present issue of Acta Physiologica , a G‐protein‐coupled receptor with known ligand, the calcium‐sensing receptor, CaSR, that is expressed abundantly in kidney and parathyroid, is now documented also in the nasal olfactory epithelium of rat, and moreover, its activation shown to initiate sympathetic efferent nerve activity to increase blood pressure and decrease perfusion of the renal, hepatic, and enteric vascular beds .…”

mentioning

confidence: 94%

Smelling through calcium‐sensing receptor affects sympathetic control of blood pressure and regional blood flow

Jensen

2018

Acta Physiologica

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T. 2018. Aromatherapy: Activating olfactory calcium-sensing receptors impairs renal hemodynamics via sympathetic nerve-mediated vasoconstriction. Acta Pysiol. 225, e13157. A number of G-protein-coupled "orphan" receptors with no known ligand have been identified in both olfactory epithelium and the kidney (for review see ref. 1) and some of them contribute to the regulation of kidney function and blood pressure. 2 In the present issue of Acta Physiologica, a G-protein-coupled receptor with known ligand, the calcium-sensing receptor, CaSR, that is expressed abundantly in kidney and parathyroid, is now documented also in the nasal olfactory epithelium of rat, and moreover, its activation shown to initiate sympathetic efferent nerve activity to increase blood pressure and decrease perfusion of the renal, hepatic, and enteric vascular beds. 3 The findings show a direct coupling between activation of the CaSR in the olfactory epithelium and increased peripheral vascular resistance by sympathetic excitation. The relevance for human vs rodent physiology, needs to be established. Moreover, concentration-response curves, the fluid-borne vs normal airborne delivery of ligand and neuroanatomical correlates need to be further explored. The reflex coupling is novel and intriguing and warrants further study of the role for nasal olfactory epithelium in blood pressure homoeostasis.In the study published in Acta, 3 Lee et al couple elegantly previous observations of manganese inhalation in mine workers causing elevated blood pressure and renal injury and that zebrafish larvae express CaSR in nasal epithelium into a mechanistic physiologic hypothesis predicting that activation of CaSR in the nasal epithelium may activate efferent sympathetic vascular nerves and thereby impact blood pressure. To test the hypothesis, they employ a rat model whereby the nasal cavity under anaesthesia is gently flushed and potential extracellular ligands-both agonists and antagonists-are delivered to the olfactory epithelium. Several control experiments were performed to assure specificity of the response. As to the sensory part, olfactory receptors comprise a large group of G-proteincoupled receptors in mammals that are expressed in the nasal olfactory epithelium and detect volatile molecules in smell but with more widespread expression across organs. As an example, the olfactory receptor Olfr78 is an oxygen sensor in the carotid body which is sensitive to the metabolite lactate and thereby controls respiration. 4 However, Olfr78, which is sensitive also to short-chain fatty acids as endogenous ligand, is also expressed in the kidney, notably in the juxtaglomerular granular cells that synthesize and release the protease renin into plasma and thereby controls activity of the circulating renin-angiotensin-aldosterone system. Olfr78 stimulation by short-chain fatty acids decreases renin secretion and, in vivo, plasma renin concentration was lower in mice stimulated by short-chain fatty acids. 2

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Unsung renal receptors: orphan G‐protein‐coupled receptors play essential roles in renal development and homeostasis

Cited by 4 publications

References 114 publications

Leukotrienes vs. Montelukast—Activity, Metabolism, and Toxicity Hints for Repurposing

Leukotrienes vs. Montelukast—Activity, Metabolism, and Toxicity Hints for Repurposing

A review of non-prostanoid, eicosanoid receptors: expression, characterization, regulation, and mechanism of action

Smelling through calcium‐sensing receptor affects sympathetic control of blood pressure and regional blood flow

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