Expression and localization of GPR91 and GPR99 in murine organs
Abstract
Energy substrates and metabolic intermediates are proven ligands of a growing number of G-protein coupled receptors. In 2004, GPR91 and GPR99 were identified as receptors for the citric acid cycle intermediates, succinate and α-ketoglutarate, respectively. GPR91 seems to act as a first responder to local stress and GPR99 participates in the regulation of the acid-base balance through an intrarenal paracrine mechanism. However, a systematic analysis of the distribution of both receptors in mouse organs is still missing. The aim of this study was to examine the expression of GPR91 and GPR99 in a large number of different murine organs both at mRNA and protein level. Whereas GPR91 mRNA was detectable in almost all organs, GPR99 mRNA was mainly expressed in neuronal tissues. Widespread expression of GPR91 was also detected at the protein level by western blotting and immunohistochemistry. In addition to neuronal cells, GPR99 protein was found in renal intercalated cells and epididymal narrow cells. Double-labeling immunohistochemistry demonstrated the colocalization of GPR99 with the B1 subunit isoform of vacuolar H(+)-ATPases which is expressed only by a very limited number of cell types. In summary, our detailed expression analysis of GPR91 and GPR99 in murine tissues will allow a more directed search for additional functions of both receptors.
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OXGR1 is widely expressed in many tissues, with adrenal glands, testes, and brain having the highest expression.
“We found that while OXGR1 is widely expressed in many tissues, adrenal glands, testes, and brain have the highest expression of GRP99, which is consistent with a previous report (Diehl et al, 2016).”
From Exercise‐induced α‐ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1‐dependent adrenal activation (2020) · cites this paper as Diehl et al, 2016
Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 2× · see citing works
“The remaining 60–70 % of variation in protein concentration is particularly caused by regulation of translation and by additional mechanisms like transcript stability and protein degradation (Schwanhäusser et al. 2011; Vogel and Marcotte 2012).”
Insights into the regulation of protein abundance from proteomic and transcriptomic analyses
Vogel, C., & Marcotte, E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3185 · Cited by 4,195 · see citing works
Interacting molecular loops in the mammalian circadian clock
Shearman, L. P., Sriram, S., Weaver, D. R., Maywood, E. S., Chaves, I., Zheng, B., Kume, K., Lee, C. C., van der, G. T. J., Horst, et al. (2000) · Science · doi:10.1126/science.288.5468.1013 · Cited by 1,367 · see citing works
Knobil and Neill's Physiology of Reproduction
(2015) · Elsevier eBooks · doi:10.1016/c2011-1-07288-0 · Cited by 1,276 · see citing works
Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors
He, W., Miao, F. J.-P., Lin, D. C.-H., Schwandner, R. T., Wang, Z., Gao, J., Chen, J.-L., Tian, H., & Ling, L. (2004) · Nature · doi:10.1038/nature02488 · Cited by 909 · see citing works
The G protein-coupled receptor repertoires of human and mouse
Vassilatis, D. K., Hohmann, J. G., Zeng, H., Li, F., Ranchalis, J., Mortrud, M. T., Brown, A., Rodriguez, S. S., Weller, J. R., Wright, A. C., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0230374100 · Cited by 779 · see citing works
Anatomical Profiling of G Protein-Coupled Receptor Expression
Regard, J. B., Sato, I. T., & Coughlin, S. R. (2008) · Cell · doi:10.1016/j.cell.2008.08.040 · Cited by 696 · see citing works
Biologically active polypeptides in submandibular glands.
Barka, T. (1980) · Journal of Histochemistry & Cytochemistry · doi:10.1177/28.8.7003006 · Cited by 470 · see citing works
The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis
Sapieha, P., Sirinyan, M., Hamel, D., Zaniolo, K., Joyal, J.-S., Cho, J.-H., Honoré, J.-C., Kermorvant-Duchemin, E., Varma, D. R., Tremblay, S., et al. (2008) · Nature Medicine · doi:10.1038/nm.1873 · Cited by 359 · see citing works
Toma, I., Kang, J. J., Sipos, A., Vargas, S., Bansal, E., Hanner, F., Meer, E., & Peti-Peterdi, J. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33293 · Cited by 322 · see citing works
Expression of nitric oxide synthase in kidney macula densa cells
Mundel, P. H., Bachmann, S., Bäder, M., et al. (1992) · Kidney International · doi:10.1038/ki.1992.382 · Cited by 297 · see citing works
Understanding the human salivary metabolome
Takeda, I., Stretch, C., Barnaby, P., Bhatnager, K., Rankin, K. N., Fu, H., Weljie, A. M., Jha, N., & Slupsky, C. M. (2009) · NMR in Biomedicine · doi:10.1002/nbm.1369 · Cited by 188 · see citing works
Kanaoka, Y., Maekawa, A., & Austen, K. F. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.c113.453704 · Cited by 186 · see citing works
Intercalated Cell Subtypes in Connecting Tubule and Cortical Collecting Duct of Rat and Mouse
Kim, J., Kim, Y., Cha, J., et al. (1999) · Journal of the American Society of Nephrology · doi:10.1681/asn.v1011 · Cited by 177 · see citing works
Robaire, B., Hinton, B. T., & Orgebin‐Crist, M. (2006) · Elsevier eBooks · doi:10.1016/b978-012515400-0/50027-0 · Cited by 177 · see citing works
Dunn, W. B., Broadhurst, D., Deepak, S. M., Buch, M. H., McDowell, G., Spasić, ., Ellis, D. I., Brooks, N. H., Kell, D. B., & Neyses, L. (2007) · Metabolomics · doi:10.1007/s11306-007-0063-5 · Cited by 174 · see citing works
Kushnir, M. M., Komaromy-Hiller, G., Shushan, B. I., Urry, F. M., & Roberts, W. L. (2001) · Clinical Chemistry · doi:10.1093/clinchem/47.11.1993 · Cited by 170 · see citing works
Circulating Succinate is Elevated in Rodent Models of Hypertension and Metabolic Disease
Sadagopan, N., Li, W., Roberds, S. L., Major, T. C., Preston, G. M., Yu, Y., & Tones, M. A. (2007) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2007.05.010 · Cited by 164 · see citing works
The Year In G Protein-Coupled Receptor Research
Millar, R. P., & Newton, C. L. (2009) · Molecular Endocrinology · doi:10.1210/me.2009-0473 · Cited by 163 · see citing works
Urine Metabolomic Analysis Identifies Potential Biomarkers and Pathogenic Pathways in Kidney Cancer
Kim, K., Taylor, S. L., Ganti, S. N., Guo, L., Osier, M. V., & Weiss, R. H. (2011) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2010.0094 · Cited by 160 · see citing works
Activation of the Succinate Receptor GPR91 in Macula Densa Cells Causes Renin Release
Vargas, S. L., Toma, I., Kang, J. J., Meer, E. J., & Peti‐Peterdi, J. (2009) · Journal of the American Society of Nephrology · doi:10.1681/asn.2008070740 · Cited by 153 · see citing works
Succinate is a paracrine signal for liver damage
Correa, P. R. A. V., Kruglov, E. A., Thompson, M., Leite, M. F., Dranoff, J. A., & Nathanson, M. H. (2007) · Journal of Hepatology · doi:10.1016/j.jhep.2007.03.016 · Cited by 151 · see citing works
Circulating anions usually associated with the Krebs cycle in patients with metabolic acidosis
Forni, L. G., McKinnon, W., Lord, G. A., et al. (2005) · Critical Care · doi:10.1186/cc3806 · Cited by 137 · see citing works
Regulation of luminal acidification in the male reproductive tract via cell–cell crosstalk
Shum, W. W., Silva, N. D., Brown, D., & Breton, S. (2009) · Journal of Experimental Biology · doi:10.1242/jeb.027284 · Cited by 134 · see citing works
Drug transporters, the blood-testis barrier and spermatogenesis
Su, L., Mruk, D. D., & Cheng, C. Y. (2010) · Journal of Endocrinology · doi:10.1677/joe-10-0363 · Cited by 123 · see citing works
Epididymal expression of the forkhead transcription factor Foxi1 is required for male fertility
Blomqvist, S. R., Viđarsson, H., Söder, O., & Enerbäck, S. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601272 · Cited by 119 · see citing works
GPCR deorphanizations: the novel, the known and the unexpected transmitters
Civelli, O. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.11.005 · Cited by 117 · see citing works
Robben, J. H., Fenton, R. A., Vargas, S. L., Schweer, H., Peti‐Peterdi, J., Deen, P. M. T., & Milligan, G. (2009) · Kidney International · doi:10.1038/ki.2009.360 · Cited by 113 · see citing works
Miller, R. L., Zhang, P., Smith, M. L., et al. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00084.2004 · Cited by 107 · see citing works
Rodríguez‐Gallego, E., Guirro, M., Riera-Borrull, M., Hernández‐Aguilera, A., Mariné-Casadó, R., Fernández‐Arroyo, S., Beltrán‐Debón, R., Sabench, F., Hernández, M., Castillo, D. D., et al. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.53 · Cited by 84 · see citing works
α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism
Tokonami, N., Morla, L., Centeno, G., Mordasini, D., Ramakrishnan, S. K., Nikolaeva, S. D., Wagner, C. A., Bonny, O., Houillier, P., Doucet, A., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67562 · Cited by 78 · see citing works
Development of renin expression in the mouse kidney
Sauter, A. W., Machura, K., Neubauer, B., et al. (2007) · Kidney International · doi:10.1038/sj.ki.5002571 · Cited by 69 · see citing works
Zhao, L., Gao, H., Lian, F., et al. (2011) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00551.2010 · Cited by 68 · see citing works
Broschat, K. O., Stidwill, R. P., & Burgess, D. R. (1983) · Cell · doi:10.1016/0092-8674(83)90190-3 · Cited by 60 · see citing works
Jayasinghe, N., Cope, G. H., & Jacob, S. (1990) · PubMed · Cited by 49 · see citing works
Hypoxia-induced increase of endostatin in murine aorta and lung
Paddenberg, R., Faulhammer, P., Goldenberg, A., & Kummer, W. (2006) · Histochemistry and Cell Biology · doi:10.1007/s00418-006-0158-5 · Cited by 45 · see citing works
Self-citationThe Epididymis: Embryology, Structure, Function And Its Role In Fertilization And Infertility
Arrotia, K., Garcia, P., Barbieri, M. F., et al. (2012) · InTech eBooks · doi:10.5772/35847 · Cited by 35 · see citing works
A novel model of spontaneous otitis media with effusion (OME) in the Oxgr1 knock-out mouse
Kerschner, J. E., Kerschner, J. E., Hong, W., et al. (2012) · International Journal of Pediatric Otorhinolaryngology · doi:10.1016/j.ijporl.2012.09.037 · Cited by 31 · see citing works
DETECTION OF RENIN mRNA IN MOUSE KIDNEY AND SUBMANDIBULAR GLAND BY HYBRIDIZATION WITH RENIN cDNA*
Mesterovic, N., Catanzaro, D. F., & Morris, B. J. (1983) · Endocrinology · doi:10.1210/endo-113-3-1179 · Cited by 26 · see citing works
Paddenberg, R., Tiefenbach, M., Faulhammer, P., Goldenberg, A., Gries, B., Pfeil, U., Lips, K. S., Piruat, J. I., López‐Barneo, J., SCHERMULY, R. T., et al. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvr359 · Cited by 22 · see citing works
Self-citationMetabolic Aspects of Spermatogenesis1
Davis, J. R. (1969) · Biology of Reproduction · doi:10.1095/biolreprod1.supplement_1.93 · Cited by 20 · see citing works
Rougeot, C., Rosinski‐Chupin, I., & Rougeot, F. (1998) · Biomedical Reviews · doi:10.14748/bmr.v9.133 · Cited by 18 · see citing works
Development, Differentiation and Derivatives of the Wolffian and Müllerian Ducts
Jacob, M. I., Yusuf, F., & Jrgen, H. (2012) · InTech eBooks · doi:10.5772/34351 · Cited by 14 · see citing works
Hypobaric hypoxia affects endogenous levels of α-keto acids in murine heart ventricles
Mühling, J., Paddenberg, R., Hempelmann, G., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.02.054 · Cited by 13 · see citing works
Self-citationRenal V‐ATPase: Physiology and Pathophysiology
Brown, D. J., & Marshansky, V. N. (2004) · doi:10.1002/3527606122.ch17 · Cited by 9 · see citing works
Treuting, P. M., & Dintzis, S. M. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-381361-9.00008-1 · Cited by 9 · see citing works
Ahmed, S. S. S. J. (2013) · Metabolomics · doi:10.1007/s11306-013-0551-8 · Cited by 6 · see citing works
Introduction of Organic Anion Transporters (SLC22A) and a Regulatory Mechanism by Caveolins
Lee, W. K., Jung, S., Kwak, J., et al. (2006) · Electrolytes & Blood Pressure · doi:10.5049/ebp.2006.4.1.8 · Cited by 6 · see citing works
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Yuan, Y., Xu, P., Jiang, Q., Cai, X., Wang, T., Peng, W., Sun, J., Zhu, C., Zhang, C., Yue, D., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2019103304 · Cited by 92 · see citing works
Cai, X., Yuan, Y., Liao, Z., Xing, K., Zhu, C., Xu, Y., Yu, L., Wang, L., Wang, S., Zhu, X., et al. (2018) · The FASEB Journal · doi:10.1096/fj.201700670r · Cited by 65 · see citing works
Cai, X., Zhu, C., Xu, Y., Jing, Y., Yuan, Y., Wang, L., Wang, S., Zhu, X., Gao, P., Zhang, Y., et al. (2016) · Scientific Reports · doi:10.1038/srep26802 · Cited by 54 · see citing works
Retracted
- Authors
- Diehl, J., Gries, B., Pfeil, U., Goldenberg, A., Mermer, P., Kummer, W., & Paddenberg, R.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- Corresponding author
- Paddenberg, Renate
- Venue
- Cell and Tissue Research
- Published
- 2015-11-21
- Volume
- 364
- Issue
- 2
- Pages
- 245-262
- ISSN
- 0302-766X (ISSN-L)
- 1432-0878
- OpenAlex
- W2240366577
- Cited by
- 50
- References
- 48
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 3
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell and Tissue Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Health Sciences › Medicine › Nephrology › Renal function and acid-base balance
- Keywords
- GPR91, G protein-coupled receptors, succinate receptor, citric acid cycle intermediates, acid-base balance, neuronal expression
- MeSH terms
- Adrenal Glands, Animals, Gastric Mucosa, Immunohistochemistry, Intestinal Mucosa, Kidney, Mice, Inbred C57BL, RNA, Messenger, Stress, Physiological, Submandibular Gland, Receptors, Purinergic P2, Reverse Transcriptase Polymerase Chain Reaction, Receptors, G-Protein-Coupled, Mice
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