A polyspecific drug/proton antiporter mediates diphenhydramine and clonidine transport at the mouse blood-retinal barrier

British Journal of Pharmacology

Volumn 172, Issue 19, 2015, Pages 4714-4725

  Chapy, Hélène ^a,b   André, Pascal ^a,b   Declèves, Xavier ^a,b,c   Scherrmann, Jean Michel ^a,b,c   Cisternino, Salvatore ^a,b,c  

^a UMR S 1144   (France)

^b UNIVERSITÉ PARIS DESCARTES   (France)

^c ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIARRHYTHMIC AGENT; ANTIDEPRESSANT AGENT; ANTIEMETIC AGENT; ANTIHISTAMINIC AGENT; ANTIMALARIAL AGENT; CLONIDINE; DIPHENHYDRAMINE; OPIATE; ORGANIC CATION TRANSPORTER 1; ORGANIC CATION TRANSPORTER 2; ORGANIC CATION TRANSPORTER 3; POTASSIUM PROTON EXCHANGE PROTEIN; PSYCHOSTIMULANT AGENT; SODIUM PROTON EXCHANGE PROTEIN; ANTIPORTER;

ACIDIFICATION; ALKALINIZATION; ANALYSIS OF VARIANCE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD RETINA BARRIER; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG DELIVERY SYSTEM; DRUG TRANSPORT; FLOW RATE; HEART PERFUSION; HUMIDITY; IN VIVO STUDY; MALE; MEMBRANE PERMEABILITY; MOUSE; NEUROMODULATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; TISSUE DISTRIBUTION; ANIMAL; KNOCKOUT MOUSE; METABOLISM; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; ANTIPORTERS; BIOLOGICAL TRANSPORT; BLOOD-RETINAL BARRIER; CLONIDINE; DIPHENHYDRAMINE; MALE; MICE; MICE, KNOCKOUT;

EID: 84940954377     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.13246     Document Type: Article

References (44)

1. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ, (2010). Structure and function of the blood-brain barrier. Neurobiol Dis 37: 13-25.
2. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013). The concise guide to pharmacology 2013/14: transporters. Br J Pharmacol 170: 1706-1796.
3. Andre P, Debray M, Scherrmann JM, Cisternino S, (2009). Clonidine transport at the mouse blood-brain barrier by a new H+ antiporter that interacts with addictive drugs. J Cereb Blood Flow Metab 29: 1293-1304.
4. Andre P, Saubamea B, Cochois-Guegan V, Marie-Claire C, Cattelotte J, Smirnova M, et al. (2012). Transport of biogenic amine neurotransmitters at the mouse blood-retina and blood-brain barriers by uptake1 and uptake2. J Cereb Blood Flow Metab 32: 1989-2001.
5. Au-Yeung SC, Rurak DW, Gruber N, Riggs KW, (2006). A pharmacokinetic study of diphenhydramine transport across the blood-brain barrier in adult sheep: potential involvement of a carrier-mediated mechanism. Drug Metab Dispos 34: 955-960.
6. Augustin R, (2010). The protein family of glucose transport facilitators: It's not only about glucose after all. IUBMB Life 62: 315-333.
7. Bush WD, Garguilo J, Zucca FA, Albertini A, Zecca L, Edwards GS, et al. (2006). The surface oxidation potential of human neuromelanin reveals a spherical architecture with a pheomelanin core and a eumelanin surface. Proc Natl Acad Sci U S A 103: 14785-14789.
8. Cattelotte J, Andre P, Ouellet M, Bourasset F, Scherrmann JM, Cisternino S, (2008). In situ mouse carotid perfusion model: glucose and cholesterol transport in the eye and brain. J Cereb Blood Flow Metab 28: 1449-1459.
9. Chapy H, Smirnova M, Andre P, Schlatter J, Chiadmi F, Couraud PO, et al. (2014). Carrier-mediated cocaine transport at the blood-brain barrier as a putative mechanism in addiction liability. Int J Neuropsychopharmacol 18. doi: 10.1093/ijnp/pyu001.
10. Chapy H, Goracci L, Vayer P, Parmentier Y, Carrupt PA, Decleves X, et al. (2015). Pharmacophore-based discovery of inhibitors of a novel drug proton-antiporter in human brain endothelial hCMEC/D3 cell line. Br J Pharmacol. doi: 10.1111/bph.13258.
11. Cisternino S, Rousselle C, Debray M, Scherrmann JM, (2004). In situ transport of vinblastine and selected P-glycoprotein substrates: implications for drug-drug interactions at the mouse blood-brain barrier. Pharm Res 21: 1382-1389.
12. Cisternino S, Chapy H, Andre P, Smirnova M, Debray M, Scherrmann JM, (2013). Coexistence of passive and proton antiporter-mediated processes in nicotine transport at the mouse blood-brain barrier. AAPS J 15: 299-307.
13. Crassous PA, Denis C, Paris H, Senard JM, (2007). Interest of alpha2-adrenergic agonists and antagonists in clinical practice: background, facts and perspectives. Curr Top Med Chem 7: 187-194.
14. Fischer W, Metzner L, Hoffmann K, Neubert RH, Brandsch M, (2006). Substrate specificity and mechanism of the intestinal clonidine uptake by Caco-2 cells. Pharm Res 23: 131-137.
15. Giacomini KM, Consortium IT, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, et al. (2010). Membrane transporters in drug development. Nat Rev Drug Discov 9: 215-236.
16. Goldberg MJ, Spector R, Chiang CK, (1987). Transport of diphenhydramine in the central nervous system. J Pharmacol Exp Ther 240: 717-722.
17. Han YH, Sweet DH, Hu DN, Pritchard JB, (2001). Characterization of a novel cationic drug transporter in human retinal pigment epithelial cells. J Pharmacol Exp Ther 296: 450-457.
18. Kalvass JC, Maurer TS, Pollack GM, (2007). Use of plasma and brain unbound fractions to assess the extent of brain distribution of 34 drugs: comparison of unbound concentration ratios to in vivo p-glycoprotein efflux ratios. Drug Metab Dispos 35: 660-666.
19. Kell DB, Dobson PD, Bilsland E, Oliver SG, (2013). The promiscuous binding of pharmaceutical drugs and their transporter-mediated uptake into cells: what we (need to) know and how we can do so. Drug Discov Today 18: 218-239.
20. Kenyon E, Maminishkis A, Joseph DP, Miller SS, (1997). Apical and basolateral membrane mechanisms that regulate pHi in bovine retinal pigment epithelium. Am J Physiol 273 (2 Pt 1): C456-C472.
21. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, (2010). Animal research: Reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 160: 1577-1579.
22. King G, Yerger VB, Whembolua GL, Bendel RB, Kittles R, Moolchan ET, (2009). Link between facultative melanin and tobacco use among African Americans. Pharmacol Biochem Behav 92: 589-596.
23. Kitamura A, Higuchi K, Okura T, Deguchi Y, (2014). Transport characteristics of tramadol in the blood-brain barrier. J Pharm Sci 103: 3335-3341.
24. Kubo Y, Tsuchiyama A, Shimizu Y, Akanuma SI, Hosoya KI, (2014). Involvement of carrier-mediated transport in the retinal uptake of clonidine at the inner blood-retinal barrier. Mol Pharm 11: 3747-3753.
25. Kuwayama K, Inoue H, Kanamori T, Tsujikawa K, Miyaguchi H, Iwata Y, et al. (2008). Uptake of 3,4-methylenedioxymethamphetamine and its related compounds by a proton-coupled transport system in Caco-2 cells. Biochim Biophys Acta 1778: 42-50.
26. Leblanc B, Jezequel S, Davies T, Hanton G, Taradach C, (1998). Binding of drugs to eye melanin is not predictive of ocular toxicity. Regul Toxicol Pharmacol 28: 124-132.
27. Lin H, Kenyon E, Miller SS, (1992). Na-dependent pHi regulatory mechanisms in native human retinal pigment epithelium. Invest Ophthalmol Vis Sci 33: 3528-3538.
28. McGrath J, Drummond G, McLachlan E, Kilkenny C, Wainwright C, (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol 160: 1573-1576.
29. Mizuuchi H, Katsura T, Ashida K, Hashimoto Y, Inui K, (2000). Diphenhydramine transport by pH-dependent tertiary amine transport system in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol 278: G563-G569.
30. Newman EA, (2013). Functional hyperemia and mechanisms of neurovascular coupling in the retinal vasculature. J Cereb Blood Flow Metab 33: 1685-1695.
31. Ochrietor JD, Clamp MF, Moroz TP, Grubb JH, Shah GN, Waheed A, et al. (2005). Carbonic anhydrase XIV identified as the membrane CA in mouse retina: strong expression in Müller cells and the RPE. Exp Eye Res 81: 492-500.
32. Okura T, Hattori A, Takano Y, Sato T, Hammarlund-Udenaes M, Terasaki T, et al. (2008). Involvement of the pyrilamine transporter, a putative organic cation transporter, in blood-brain barrier transport of oxycodone. Drug Metab Dispos 36: 2005-2013.
33. Pawson AJ, Sharman JL, Benson HE, Faccenda E, Alexander SP, Buneman OP, et al.; NC-IUPHAR. (2014) The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands. Nucl Acids Res 42 (Database Issue): D1098-D1106.
34. Pomerleau AC, Gooden CE, Fantz CR, Morgan BW, (2014). Dermal exposure to a compounded pain cream resulting in severely elevated clonidine concentration. J Med Toxicol 10: 61-64.
35. Pragst F, Herre S, Bakdash A, (2006). Poisonings with diphenhydramine-a survey of 68 clinical and 55 death cases. Forensic Sci Int 161: 189-197.
36. Ronaldson PT, Davis TP, (2013). Targeted drug delivery to treat pain and cerebral hypoxia. Pharmacol Rev 65: 291-314.
37. Roth M, Obaidat A, Hagenbuch B, (2012). OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br J Pharmacol 165: 1260-1287.
38. Rumsey SC, Kwon O, Xu GW, Burant CF, Simpson I, Levine M, (1997). Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J Biol Chem 272: 18982-18989.
39. Sadiq MW, Borgs A, Okura T, Shimomura K, Kato S, Deguchi Y, et al. (2011). Diphenhydramine active uptake at the blood-brain barrier and its interaction with oxycodone in vitro and in vivo. J Pharm Sci 100: 3912-3923.
40. Seelig A, Gottschlich R, Devant RM, (1994). A method to determine the ability of drugs to diffuse through the blood-brain barrier. Proc Natl Acad Sci U S A 91: 68-72.
41. Takasato Y, Rapoport SI, Smith QR, (1984). An in situ brain perfusion technique to study cerebrovascular transport in the rat. Am J Physiol 247 (3 Pt 2): H484-H493.
42. Taylor CJ, Nicola PA, Wang S, Barrand MA, Hladky SB, (2006). Transporters involved in regulation of intracellular pH in primary cultured rat brain endothelial cells. J Physiol 576 (Pt 3): 769-785.
43. Zane PA, Brindle SD, Gause DO, O'Buck AJ, Raghavan PR, Tripp SL, (1990). Physicochemical factors associated with binding and retention of compounds in ocular melanin of rats: correlations using data from whole-body autoradiography and molecular modeling for multiple linear regression analyses. Pharm Res 7: 935-941.
44. Zhang N, Kannan R, Okamoto CT, Ryan SJ, Lee VH, Hinton DR, (2006). Characterization of brimonidine transport in retinal pigment epithelium. Invest Ophthalmol Vis Sci 47: 287-294.