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The Organic Anion Transporter (OAT) Family: A Systems Biology Perspective
Open accessAbstract
The organic anion transporter (OAT) subfamily, which constitutes roughly half of the SLC22 (solute carrier 22) transporter family, has received a great deal of attention because of its role in handling of common drugs (antibiotics, antivirals, diuretics, nonsteroidal anti-inflammatory drugs), toxins (mercury, aristolochic acid), and nutrients (vitamins, flavonoids). Oats are expressed in many tissues, including kidney, liver, choroid plexus, olfactory mucosa, brain, retina, and placenta. Recent metabolomics and microarray data from Oat1 [ Slc22a6, originally identified as NKT (novel kidney transporter)] and Oat3 ( Slc22a8) knockouts, as well as systems biology studies, indicate that this pathway plays a central role in the metabolism and handling of gut microbiome metabolites as well as putative uremic toxins of kidney disease. Nuclear receptors and other transcription factors, such as Hnf4α and Hnf1α, appear to regulate the expression of certain Oats in conjunction with phase I and phase II drug metabolizing enzymes. Some Oats have a strong selectivity for particular signaling molecules, including cyclic nucleotides, conjugated sex steroids, odorants, uric acid, and prostaglandins and/or their metabolites. According to the “Remote Sensing and Signaling Hypothesis,” which is elaborated in detail here, Oats may function in remote interorgan communication by regulating levels of signaling molecules and key metabolites in tissues and body fluids. Oats may also play a major role in interorganismal communication (via movement of small molecules across the intestine, placental barrier, into breast milk, and volatile odorants into the urine). The role of various Oat isoforms in systems physiology appears quite complex, and their ramifications are discussed in the context of remote sensing and signaling.
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Items 201–267 of 267
Sakiyama, M., Matsuo, H., Shimizu, S., Nakashima, H., Nakayama, A., Chiba, T., Naito, M., Takada, T., Suzuki, H., Hamajima, N., et al. (2013) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.dmpk-13-nt-070 · Cited by 57
Žlender, V., Breljak, D., Ljubojević, M., Flajs, D., Balen, D., Brzica, H., Domijan, A., Peraica, M., Fuchs, R., & Anzai, N. (2009) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2009.06.008 · Cited by 56
Intracellular compartmentation of organic anions within renal cells
Miller, D. S., Stewart, D. E., & Pritchard, J. B. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.264.5.r882 · Cited by 53
Sauvant, C., Holzinger, H., & Gekle, M. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005070727 · Cited by 52
Karns, R. A., Zhang, G., Sun, G., Indugula, S. R., Cheng, H., Auguštin, D. H., Novokmet, N., Rudan, D., Duraković, Z., Missoni, S., et al. (2012) · Annals of Human Genetics · doi:10.1111/j.1469-1809.2011.00698.x · Cited by 52
Miyajima, M., Kusuhara, H., Fujishima, M., Adachi, Y., & Sugiyama, Y. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.110.036863 · Cited by 50
Pombrio, J. M., Giangreco, A., Li, L., Wempe, M. F., Anders, M. W., Sweet, D. H., Pritchard, J. B., & Ballatori, N. (2001) · Molecular Pharmacology · doi:10.1124/mol.60.5.1091 · Cited by 50
Presence of organic anion transporters 3 (OAT3) and 4 (OAT4) in human adrenocortical cells
Asif, A. R., Steffgen, J., Metten, M., Grunewald, R. W., Muller, G. A., Bahn, A., Burckhardt, G., & Hagos, Y. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-004-1373-3 · Cited by 49
Uwai, Y., Motohashi, H., Tsuji, Y., Ueo, H., Katsura, T., & Inui, K. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.03.024 · Cited by 47
Vitetta, L., Linnane, A. W., & Gobe, G. C. (2013) · Toxins · doi:10.3390/toxins5112042 · Cited by 47
Evidence that brain prostaglandin E2 is involved in physiological sleep-wake regulation in rats.
Matsumura, H., Honda, K., Choi, W. S., Inoué, S., Sakai, T., & Hayaishi, O. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.14.5666 · Cited by 46
Transport of estrone sulfate by the novel organic anion transporter Oat6 (Slc22a20)
Schnabolk, G., Youngblood, G. L., & Sweet, D. H. (2006) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00497.2005 · Cited by 46
Analyses of 5′ regulatory region polymorphisms in human SLC22A6 (OAT1) and SLC22A8 (OAT3)
Bhatnagar, V., Xu, G., Hamilton, B. A., Truong, D. M., Eraly, S. A., Wu, W., & Nigám, S. K. (2006) · Journal of Human Genetics · doi:10.1007/s10038-006-0398-1 · Cited by 45
Self-citationKobayashi, Y., Ohshiro, N., Tsuchiya, A., Kohyama, N., Ohbayashi, M., & Yamamoto, T. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.32.5.479 · Cited by 44
Adaptive responses of renal organic anion transporter 3 (OAT3) during cholestasis
Chen, J., Terada, T., Ogasawara, K., Katsura, T., & Inui, K. (2008) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00139.2008 · Cited by 44
Tachikawa, M., Ozeki, G., Higuchi, T., Akanuma, S., Tsuji, K., & Hosoya, K. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12018 · Cited by 44
Sugawara, M., Mochizuki, T., Takekuma, Y., & Miyazaki, K. (2005) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2005.06.006 · Cited by 43
Hagos, Y., Krick, W., Braulke, T., Mühlhausen, C., Burckhardt, G., & Burckhardt, B. C. (2008) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-008-0489-2 · Cited by 43
Novel aspects of renal organic anion transporters
Eraly, S. A., Blantz, R. C., Bhatnagar, V., & Nigám, S. K. (2003) · Current Opinion in Nephrology & Hypertension · doi:10.1097/00041552-200309000-00011 · Cited by 40
Self-citationGallegos, T. F., Martovetsky, G., Kouznetsova, V. L., Bush, K. T., & Nigám, S. K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040796 · Cited by 39
Self-citationYokoyama, H., Anzai, N., Ljubojević, M., Ohtsu, N., Sakata, T., Miyazaki, H., Nonoguchi, H., Islam, M. R., Onozato, M., Tojo, A., et al. (2008) · Cellular Physiology and Biochemistry · doi:10.1159/000129385 · Cited by 38
Zhou, F., Xu, W., Tanaka, K., & You, G. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9359-4 · Cited by 38
DEAN, S., Tang, J. I.-S., Seckl, J. R., & Nyirenda, M. (2010) · Gene Expression · doi:10.3727/105221610x12717040569901 · Cited by 37
Biology of Fluoro-Organic Compounds
Zhang, X., Lai, T., & Kong, R. Y. C. (2011) · Topics in current chemistry · doi:10.1007/128_2011_270 · Cited by 36
Eder, K., & Ringseis, R. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.11.042 · Cited by 36
Functional characterization of a human organic anion transporter hOAT4 in placental BeWo cells
Zhou, F., Illsley, N. P., & You, G. (2005) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2005.09.008 · Cited by 36
Establishment and Analysis ofSLC22A12(URAT1) Knockout Mouse
Hosoyamada, M., Takiue, Y., Morisaki, H., Cheng, J., Ikawa, M., Okabe, M., Morisaki, T., Ichida, K., Hosoya, T., & Shibasaki, T. (2010) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1080/15257771003738634 · Cited by 35
López-Nieto, C. E., & Nigám, S. K. (1996) · Nature Biotechnology · doi:10.1038/nbt0796-857 · Cited by 35
Taleb, O., Maammar, M., Brumaru, D., Bourguignon, J., Schmitt, M., Klein, C., Kemmel, V., Maître, M., & Mensah‐Nyagan, A. G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048553 · Cited by 35
Wang, J.-S., Newport, D. J., Stowe, Z. N., Donovan, J. L., Pennell, P. B., & DeVane, C. L. (2007) · Drug Metabolism Reviews · doi:10.1080/03602530701690390 · Cited by 35
Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis
Brandoni, A. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i44.6387 · Cited by 35
Nishiwaki, T., Daigo, Y., Tamari, M., Fujii, Y., & Nakamura, Y. (1998) · Cytogenetic and Genome Research · doi:10.1159/000015197 · Cited by 34
Analysis of Metagene Portraits Reveals Distinct Transitions During Kidney Organogenesis
Tsigelny, I. F., Kouznetsova, V. L., Sweeney, D. E., Wu, W., Bush, K. T., & Nigám, S. K. (2008) · Science Signaling · doi:10.1126/scisignal.1163630 · Cited by 34
Self-citationMizuno, N., Takahashi, T., Iwase, Y., Kusuhara, H., Niwa, T., & Sugiyama, Y. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.106.013912 · Cited by 34
Characterization of mouse organic anion transporter 5 as a renal steroid sulfate transporter
Kwak, J., Kim, H.-W., Oh, K.-J., Ko, C.-B., Park, H., & Ho, S. (2005) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2005.06.028 · Cited by 32
Klein, K., Jüngst, C., Mwinyi, J., Stieger, B., Krempler, F., Patsch, W., Eloranta, J. J., & Kullak-Ublick, G. A. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.065201 · Cited by 32
Genetic Impact on Uric Acid Concentration and Hyperuricemia in the Japanese Population
Takeuchi, F., Yamamoto, K., Isono, M., Katsuya, T., Akiyama, K., Ohnaka, K., Rakugi, H., Yamori, Y., Ogihara, T., Takayanagi, R., et al. (2012) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.15727 · Cited by 31
Hatano, R., Onoe, K., Obara, M., Matsubara, M., Kanai, Y., Muto, S., & Asano, S. (2011) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00366.2011 · Cited by 31
Zalups, R. K., & Ahmad, S. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.090530 · Cited by 31
Breljak, D., Ljubojević, M., Balen, D., Žlender, V., Brzica, H., Micek, V., Kušan, M., Anzai, N., & Sabolić, I. (2010) · PubMed · doi:10.14670/hh-25.1385 · Cited by 30
Iacobucci, I., Lonetti, A., Candoni, A., Sazzini, M., Papayannidis, C., Formica, S., Ottaviani, E., Ferrari, A., Michelutti, A., Simeone, E., et al. (2012) · The Pharmacogenomics Journal · doi:10.1038/tpj.2012.13 · Cited by 29
Li, S., Zhang, Q., & You, G. (2013) · Molecular Pharmacology · doi:10.1124/mol.113.086769 · Cited by 29
Expression and function of Oat1 and Oat3 in rat kidney exposed to mercuric chloride
Giusto, G. D., Anzai, N., Ruiz, M. L., Endou, H., & Torres, A. M. (2009) · Archives of Toxicology · doi:10.1007/s00204-009-0445-8 · Cited by 28
Yamashita, F., Ohtani, H., Koyabu, N., Ushigome, F., Satoh, H., 村上, 秀., Uchiumi, T., Nakamura, T., Kuwano, M., Tsujimoto, M., et al. (2006) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.58.11.0011 · Cited by 28
Wu, W., Baker, M. E., Eraly, S. A., Bush, K. T., & Nigám, S. K. (2009) · Physiological Genomics · doi:10.1152/physiolgenomics.90309.2008 · Cited by 28
Self-citationShuster, D. L., Bammler, T., Beyer, R., MacDonald, J. W., Tsai, J. M., Farin, F., Hebert, M., Thummel, K., & Mao, Q. (2013) · Drug Metabolism And Disposition · doi:10.1124/dmd.112.049718 · Cited by 28
Update on the molecular physiology of organic anion transporters
Ahn, S.-Y., & Bhatnagar, V. (2008) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e32830b5d5d · Cited by 27
Self-citationOrganic anion transporter OAT1 is involved in renal handling of citrulline
Nakakariya, M., Shima, Y., Shirasaka, Y., Mitsuoka, K., Nakanishi, T., & Tamai, I. (2009) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.90662.2008 · Cited by 27
Chahine, S., Campos, A., & O’Donnell, M. J. (2012) · Journal of Experimental Biology · doi:10.1242/jeb.071100 · Cited by 26
Wegner, W., Burckhardt, B. C., Burckhardt, G., & Henjakovic, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035556 · Cited by 25
Chahine, S., Seabrooke, S., & O’Donnell, M. J. (2012) · Archives of Insect Biochemistry and Physiology · doi:10.1002/arch.21066 · Cited by 24
Upregulation of mammary gland OCTNs maintains carnitine homeostasis in suckling infants
Lamhonwah, A., Mai, L., Chung, C., Lamhonwah, D., Ackerley, C. A., & Tein, I. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.12.100 · Cited by 24
Schnabolk, G., Gupta, B., Mulgaonkar, A., Kulkarni, M. P., & Sweet, D. H. (2010) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.168765 · Cited by 24
Wang, L., & Sweet, D. H. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/612527 · Cited by 24
Yang, J., Kalogerou, M., Gallacher, J., Sampson, J. R., & Shen, M. H. (2012) · European Journal of Cancer · doi:10.1016/j.ejca.2012.10.027 · Cited by 22
Tsuchida, H., Anzai, N., Shin, H., Wempe, M. F., Jutabha, P., Enomoto, A., Cha, S., Satoh, T., Ishida, M., Sakurai, H., et al. (2010) · Cellular Physiology and Biochemistry · doi:10.1159/000303060 · Cited by 22
Kittayaruksakul, S., Soodvilai, S., Asavapanumas, N., Muanprasat, C., & Chatsudthipong, V. (2011) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00341.2011 · Cited by 21
Duan, P., Li, S., & You, G. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.070185 · Cited by 19
Tsigelny, I. F., Kovalskyy, D., Kouznetsova, V. L., Balinskyi, O., Sharikov, Y., Bhatnagar, V., & Nigám, S. K. (2011) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-011-9191-7 · Cited by 18
Self-citationGutgesell, A., Ringseis, R., Brandsch, C., Stangl, G. I., Hirche, F., & Eder, K. (2009) · Metabolism · doi:10.1016/j.metabol.2008.09.018 · Cited by 18
Short-term regulation of organic anion transporters
Duan, P., & You, G. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.08.002 · Cited by 18
Kouznetsova, V. L., Tsigelny, I. F., Nagle, M. A., & Nigám, S. K. (2011) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2011.04.045 · Cited by 15
Novel sensory signaling systems in the kidney
Pluznick, J. L., & Caplan, M. J. (2012) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e328354a6bd · Cited by 14
Metabolic syndrome and psychotropic medications.
Filaković, P., Erić, A. P., & Radanović-Grgurić, L. (2012) · PubMed · Cited by 13
Takemiya, T. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.07.001 · Cited by 8
Glucocorticoid mediates the transcription of OAT-PG, a kidney-specific prostaglandin transporter
Hatano, R., Mukouchi, H., Matsumoto, Y., Kawaguchi, K., Kazama, I., Endo, Y., Toyama, H., Ejima, Y., Kurosawa, S., Kanai, Y., et al. (2013) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-013-1351-8 · Cited by 7
Bush, K. T., Nagle, M. A., Truong, D. M., Bhatnagar, V., Kaler, G. V., Eraly, S. A., Wu, W., & Nigám, S. K. (2014) · Wiley eBooks · doi:10.1002/9781118705308.ch3 · Cited by 5
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Metadata
- Authors
- Nigam, S. K., Bush, K. T., Martovetsky, G., Ahn, S.-Y., Liu, H. C., Richard, E., Bhatnagar, V., & Wu, W.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2015-01
- Volume
- 95
- Issue
- 1
- Pages
- 83-123
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2103323995
- Cited by
- 502
- References
- 267
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- green
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