HUMAN ORGANIC SOLUTE TRANSPORTERS UTTERED IN SMALL INTESTINE, LIVER, AND KIDNEY FOR HOMEOSTASIS

  • HARANATH CHINTHAGINJALA Department of Pharmaceutics and Industrial Pharmacy, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K. R. Palli Cross, Ananthapuramu 515721, Andhra Pradesh, India
  • HINDUSTAN ABDUL AHAD Department of Pharmaceutics and Industrial Pharmacy, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K. R. Palli Cross, Ananthapuramu 515721, Andhra Pradesh, India
  • MAHESH REDDY CHALLA Department of Pharmaceutics and Industrial Pharmacy, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K. R. Palli Cross, Ananthapuramu 515721, Andhra Pradesh, India
  • GANDLA CHAITHANYA BARGHAV Department of Pharmaceutics and Industrial Pharmacy, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K. R. Palli Cross, Ananthapuramu 515721, Andhra Pradesh, India
  • PASAM DEVIKA Department of Pharmaceutics and Industrial Pharmacy, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K. R. Palli Cross, Ananthapuramu 515721, Andhra Pradesh, India
  • SRIKANTHAM SAI VIKAS Department of Pharmaceutics and Industrial Pharmacy, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K. R. Palli Cross, Ananthapuramu 515721, Andhra Pradesh, India

Abstract

The transporters participate in a significant role in drug absorption, distribution, metabolism, and elimination. Transporters are of efflux and influx type, need ATP-binding sites for their in and out movement across the cell membrane. These transporters play an important role in allowing or opposing the drugs into the cells, results in non-linearity in drug pharmacokinetics. A wide range of transporters was discovered; among them, organic solute transporters (OST) play a key role in drug absorption and disposition. Organic solute transporters is a heteromeric transporter localized to the basolateral of epithelial cells. It is the primary efflux bile acid transporter in the intestine of mammals.

Keywords: Organic solute transporters, ATP-binding site, Bile acid transporter

References

1. Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995;12:413-20.
2. Hertanto R, Bastian WP, Louisa M. The modulation of drug efflux transporter by curcumin in MCF 7 breast cancer cells after repeated exposure of endoxifen and estradiol. Int J Appl Pharm 2018;10:102-5.
3. Dawson PA, Hubbert ML, Rao A. Getting the mOST from OST: role of organic solute transporters, OST?-OST?, in bile acid and steroid metabolism. Biochim Biophys Acta Mol Cell Biol Lipids 2010;1801:994-1004.
4. Russel FG. Transporters: importance in drug absorption, distribution, and removal. In: Enzyme-and transporters-based drug-drug interactions; 2010. p. 27-49.
5. Liang Y, Li S, Chen L. The physiological role of drug transporters. Protein Cell 2015;6:334-50.
6. Petzinger E, Geyer J. Drug transporters in pharmacokinetics. Naunyn-Schmiedeberg's Arch Pharmacol 2006;372:465-75.
7. Ballatori N. Biology of a novel organic solute and steroid transporters, OST?-OST?. Exp Biol Med 2005;230:689-98.
8. Ballatori N, Christian WV, Wheeler SG, Hammond CL. The heteromeric organic solute transporters, OST?–OST?/SLC51: a transporter for steroid-derived molecules. Mol Aspects Med 2013;34:683-92.
9. Dawson PA, Hubbert ML, Rao A. Getting the mOST from OST: role of organic solute transporters, OST?-OST?, in bile acid and steroid metabolism. Biochim Biophys Acta Mol Cell Biol Lipids 2010;1801:994-1004.
10. Dawson PA, Lan T, Rao A. Bile acid transporters. J Lipid Res 2009;50:2340-57.
11. Schaffner CA, Mwinyi J, Gai Z, Thasler WE, Eloranta JJ, Kullak Ublick GA. The organic solute transporters alpha and beta are induced by hypoxia in human hepatocytes. Liver Int 2015;35:1152-61.
12. Rao A, Haywood J, Craddock AL, Belinsky MG, Kruh GD, Dawson PA. The organic solute transporters ?-?, Ost?-Ost?, is essential for intestinal bile acid transport and homeostasis. Proc Natl Acad Sci India 2008;105:3891-6.
13. Anusha GB, Hindustan AA, Haranath C, Suryaprakash RC, Kalpana K. A technical view on transporters-the drug pharmacokinetics dictators. MOJ Bioequivalence Bioavailability 2019;6:39?45.
14. Landowski CP, Sun D, Foster DR, Menon SS, Barnett JL, Welage LS. Gene expression in the human intestine and correlation with oral valacyclovir pharmacokinetic parameters. J Pharmacol Exp Ther 2003;306:778-86.
15. Shugarts S, Benet LZ. The role of transporters in the pharmacokinetics of orally administered drugs. Pharm Res 2009;26:2039-54.
16. Mizuno N, Sugiyama Y. Drug transporters: their role and importance in the selection and development of new drugs. Drug Metab Pharmacokinet 2002;17:93-108.
17. Wu CY, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res 2005;22:11-23.
18. Hagenbuch B, Gui C. Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family. Xenobiotica 2008;38:778-801.
19. Zhou SF, Wang LL, Di YM, Xue CC, Duan W, Li CG. Substrates and inhibitors of human multidrug resistance-associated proteins and the implications in drug development. Curr Med Chem 2008;15:1981-2039.
20. Nielsen S, Westerhoff AM, Ge LG, Carlsen KL, Pedersen MDL, Nielsen CU. MRP2-mediated transport of etoposide in MDCKII MRP2 cells is unaffected by commonly used non-ionic surfactants. Int J Pharm 2019;565:306-15.
21. Kusuhara H, Sugiyama Y. ATP-binding cassette, subfamily G (ABCG family). Pflugers Archiv Eur J Physiol 2007;453:735-44.
22. Srimaroeng C, Perry JL, Pritchard JB. Physiology, structure, and regulation of the cloned organic anion transporters. Xenobiotica 2008;38:889-935.
23. Zair ZM, Eloranta JJ, Stieger B, Kullak Ublick GA. Pharmacogenetics of OATP (SLC21/SLCO), OAT and OCT (SLC22) and PEPT (SLC15) transporters in the intestine, liver and kidney. Pharmacogenomics 2008;9:597-624.
24. Ciarimboli G. Organic cation transporters. Xenobiotica 2008;38:936-71.
25. Van Montfoort JE, Muller M, Groothuis GM, Meijer DK, Koepsell H, Meier PJ. Comparison of “type I” and “type II” organic cation transport by organic cation Transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther 2001;298:110-5.
26. Li L, Meier PJ, Ballatori N. Oatp2 mediates bidirectional organic solute transport: a role for intracellular glutathione. Mol Pharmacol 2000;58:335-40.
27. Satlin LM, Amin V, Wolkoff AW. Organic anion transporting polypeptide mediates organic anion/HCO3? exchange. J Biol Chem 1997;272:26340-5.
28. Rao A, Haywood J, Craddock AL, Belinsky MG, Kruh GD, Dawson PA. The organic solute transporters ?-?, Ost?-Ost?, is essential for intestinal bile acid transport and homeostasis. Proc Natl Acad Sci USA 2008;105:3891-6.
29. Soroka CJ, Mennone A, Hagey LR, Ballatori N, Boyer JL. Mouse organic solute Transporters ? deficiency enhances renal excretion of bile acids and attenuates cholestasis. Hepatology 2010;51:181-90.
30. Mahadevan MV, Ramaswamy RS, Banumathi V. Mimosa pudica exerts neuroprotection against MPP induced neurotoxicity in SH-SY5Y cell lines-an in vitro model of anti-parkinsonism. Int J Pharm Pharm Sci 2006;9:21-6.
31. Li N, Cui Z, Fang F, Lee JY, Ballatori N. Heterodimerization, trafficking and membrane topology of the two proteins, Ost? and Ost?, that constitute the organic solute and steroid transporters. Biochem J 2007;407:363-72.
32. Frankenberg T, Rao A, Chen F, Haywood J, Shneider BL, Dawson PA. Regulation of the mouse organic solute transporters ?-?, Ost?-Ost?, by bile acids. Am J Physiol Gastrointest Liver Physiol 2006;290:G912-22.
33. Landrier JF, Eloranta JJ, Vavricka SR, Kullak Ublick GA. The nuclear receptor for bile acids, FXR, transactivates the human organic solute transporters-? and-? genes. Am J Physiol Gastrointest Liver Physiol 2006;290:G476-85.
34. Sultan M, Rao A, Elpeleg O, Vaz FM, Abu Libdeh B, Karpen SJ. Organic solute transporters?? (SLC51B) deficiency in two brothers with congenital diarrhea and features of cholestasis. Hepatology 2018;68:590-8.
35. Khandelwal VK, Singh P, Ravingerova T, Chaudhary M. Evaluation of ezenus in an experimental model of diet-induced alcoholic and non-alcoholic fatty liver condition in rats. Int J Pharm Pharm Sci 2015;7:247-52.
36. Russell DW. Fifty years of advances in bile acid synthesis and metabolism. J Lipid Res 2009;50(Suppl):S120-5.
37. Malinen MM, Ali L, Bezençon J, Beaudoin JJ, Brouwer KLR. Organic solute Transporters OST?/? is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury. Am J Physiol Gastrointest Liver Physiol 2018;314:G597-G609.
38. Courtney BF, Jianing Li, Jamie H, Kimberly P, Brian SR, Benjamin H. Organic solute transporters ?-? protects ileal enterocytes from bile acid-induced injury. Cellular Mol Gastro Enterol Hepatol 2018;5:499–522.
39. Khan AA, Chow EC, Porte RJ, Pang KS, Groothuis GM. Expression and regulation of the bile acid transporters, OST??OST? in rat and human intestine and liver. Biopharm Drug Dispos 2009;30:241-58.
40. Sun AQ, Balasubramaniyan N, Xu K, Liu C, Ponamgi VM, Liu H, et al. Protein-protein interaction and membrane localization of human organic solute transporters (hOST). Am J Physiol Gastrointest Liver Physiol 2007;292:G1586–93.
41. Li N, Cui Z, Fang F, Lee JY, Ballatori N. Heterodimerization, trafficking and membrane topology of the two proteins, Ost? and Ost?, that constitute the organic solute and steroid transporters. Biochem J 2007;407:363-72.
42. Ballatori N, Christian WV, Lee JY, Dawson PA, Soroka CJ, Boyer JL. OST??OST?: A major basolateral bile acid and steroid transporters in human intestinal, renal, and biliary epithelia. Hepatology 2005;42:1270-9.
43. Melina MM, Izna Ali, Kim LR. Organic solute transporters OST?/? is verexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury. Am J Physiol Gastrointest Liver Physiol 2018;314:G597–G609.
44. Seward DJ, Koh AS, Boyer JL, Ballatori N. Functional complementation between a novel mammalian polygenic transport complex and evolutionarily ancient organic solute transporters, OST?-OST?. J Biol Chem 2003;278:27473-82.
45. Dawson PA, Haywood J, Craddock AL, Wilson M, Tietjen M, Kluckman K. Targeted deletion of the ileal bile acid transporters eliminates enterohepatic cycling of bile acids in mice. J Biol Chem 2003;278:33920-7.
46. Soroka CJ, Mennone A, Hagey LR, Ballatori N, Boyer JL. Mouse organic solute Transporters ? deficiency enhances renal excretion of bile acids and attenuates cholestasis. Hepatology 2010;51:181-90.
47. Al-mamun MA, Rahman MA, Hassan R, Rahmann Z, Haque KMF. Histopathological alterations induced by common krait bungarus caeruleus venom on hepatic, renal and cardiac tissues of albino mice. Int J Pharm Pharm Sci 2014;7:239-42.
Statistics
43 Views | 15 Downloads
Citatons
How to Cite
CHINTHAGINJALA, H., AHAD, H. A., CHALLA, M. R., BARGHAV, G. C., DEVIKA, P., & VIKAS, S. S. (2019). HUMAN ORGANIC SOLUTE TRANSPORTERS UTTERED IN SMALL INTESTINE, LIVER, AND KIDNEY FOR HOMEOSTASIS. International Journal of Applied Pharmaceutics, 11(6), 12-17. https://doi.org/10.22159/ijap.2019v11i6.35260
Section
Review Article(s)