Spatial expression and functionality of drug transporters in the intact lung: Objectives for further research

Advanced Drug Delivery Reviews

Volumn 63, Issue 1-2, 2011, Pages 110-118

  Gumbleton, Mark ^a   Al Jayyoussi, Ghaith ^a   Crandon Lewis, Adam ^a   Francombe, Danielle ^a   Kreitmeyr, Katharina ^a   Morris, Chris J ^a   Smith, Mathew W ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

ATP; BCRP; Delivery; Lung; MRP; OAT; OATP; OCT; OCTN; P glycoprotein; Pharmacokinetics; Pulmonary; Transporter

Indexed keywords

ATP; BCRP; DELIVERY; LUNG; MRP; OAT; OATP; OCT; OCTN; P-GLYCOPROTEIN; PULMONARY; TRANSPORTER;

ABSORPTION; BIOLOGICAL ORGANS; DRUG DOSAGE; ENGINEERING RESEARCH; GLYCOPROTEINS; PHARMACOKINETICS; TISSUE;

DRUG INTERACTIONS;

AMIODARONE; BETA LACTAM ANTIBIOTIC; BREAST CANCER RESISTANCE PROTEIN; DIGOXIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ELACRIDAR; FEXOFENADINE; FORMOTEROL; GLYCOPROTEIN P; IPRATROPIUM BROMIDE; LOSARTAN; MESSENGER RNA; MITOXANTRONE; MULTIDRUG RESISTANCE PROTEIN 1; OCTAMER TRANSCRIPTION FACTOR 1; OCTAMER TRANSCRIPTION FACTOR 2; OCTAMER TRANSCRIPTION FACTOR 4; ORGANIC CATION TRANSPORTER 1; ORGANIC CATION TRANSPORTER 2; PEPTIDE TRANSPORTER 2; ROSUVASTATIN; SMALL INTERFERING RNA;

ASTHMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DISPOSITION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG PENETRATION; ENZYME SPECIFICITY; GENETIC POLYMORPHISM; HUMAN; LUNG; LUNG ALVEOLUS EPITHELIUM; LUNG PERFUSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; STRUCTURE ACTIVITY RELATION; SYSTEMIC CIRCULATION;

ANIMALS; BIOLOGICAL TRANSPORT; CARRIER PROTEINS; DRUG DISCOVERY; DRUG INTERACTIONS; HUMANS; INDIVIDUALITY; LUNG; PHARMACOKINETICS;

EID: 79953025375     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.addr.2010.09.008     Document Type: Review

References (92)

1. Bosquillon C. Drug transporters in the lung-do they play a role in the biopharmaceutics of inhaled drugs?. J. Pharm. Sci. 2010, 99:2240-2255.
2. van der Deen M., de Vries E.G., Timens W., Scheper R.J., Timmer-Bosscha H., Postma D.S. ATP-binding cassette (ABC) transporters in normal and pathological lung. Respir. Res. 2005, 6:59.
3. Raub T.J. P-glycoprotein recognition of substrates and circumvention through rational drug design. Mol. Pharm. 2006, 3:3-25.
4. Stouch T.R., Gudmundsson O. Progress in understanding the structure-activity relationships of P-glycoprotein. Adv. Drug Deliv. Rev. 2002, 54:315-328.
5. Pajeva I.K., Wiese M. Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis). J. Med. Chem. 2002, 45:5671-5686.
6. Bleasby K., Castle J.C., Roberts C.J., Cheng C., Bailey W.J., Sina J.F., Kulkarni A.V., Hafey M.J., Evers R., Johnson J.M., Ulrich R.G., Slatter J.G. Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: a resource for investigations into drug disposition. Xenobiotica 2006, 36:963-988.
7. Crapo J.D., Barry B.E., Gehr P., Bachofen M., Weibel E.R. Cell number and cell characteristics of the normal human lung. Am. Rev. Respir. Dis. 1982, 126:332-337.
8. Haies D.M., Gil J., Weibel E.R. Morphometric study of rat lung cells. I. Numerical and dimensional characteristics of parenchymal cell population. Am. Rev. Respir. Dis. 1981, 123:533-541.
9. Brady J.M., Cherrington N.J., Hartley D.P., Buist S.C., Li N., Klaassen C.D. Tissue distribution and chemical induction of multiple drug resistance genes in rats. Drug Metab. Dispos. 2002, 30:838-844.
10. Campbell L., Abulrob A.N., Kandalaft L.E., Plummer S., Hollins A.J., Gibbs A., Gumbleton M. Constitutive expression of P-glycoprotein in normal lung alveolar epithelium and functionality in primary alveolar epithelial cultures. J. Pharmacol. Exp. Ther. 2003, 304:441-452.
11. Cordon-Cardo C., O'Brien J.P., Boccia J., Casals D., Bertino J.R., Melamed M.R. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J. Histochem. Cytochem. 1990, 38:1277-1287.
12. C.K.v.K., van der Valk P., Ketelaars H., Broxterman H.J., Scheffer G., Kuiper C.M., Tsuruo T., Lankelma J., Meijer C.J.L.M., Pinedo H.M., Scheper R.J. Distribution of multi-drug resistance-associated P-glycoprotein in normal and neoplastic human tissues. Ann. Oncol. 1990, 1:56-64.
13. Lechapt-Zalcman E., Hurbain I., Lacave R., Commo F., Urban T., Antoine M., Milleron B., Bernaudin J.F. MDR1-Pgp 170 expression in human bronchus. Eur. Respir. J. 1997, 10:1837-1843.
14. Scheffer G.L., Pijnenborg A.C., Smit E.F., Muller M., Postma D.S., Timens W., van der Valk P., de Vries E.G., Scheper R.J. Multidrug resistance related molecules in human and murine lung. J. Clin. Pathol. 2002, 55:332-339.
15. Endter S., Becker U., Daum N., Huwer H., Lehr C.M., Gumbleton M., Ehrhardt C. P-glycoprotein (MDR1) functional activity in human alveolar epithelial cell monolayers. Cell Tissue Res. 2007, 328:77-84.
16. Tronde A., Norden B., Marchner H., Wendel A.K., Lennernas H., Bengtsson U.H. Pulmonary absorption rate and bioavailability of drugs in vivo in rats: structure-absorption relationships and physicochemical profiling of inhaled drugs. J. Pharm. Sci. 2003, 92:1216-1233.
17. Tronde A., Norden B., Jeppsson A.B., Brunmark P., Nilsson E., Lennernas H., Bengtsson U.H. Drug absorption from the isolated perfused rat lung-correlations with drug physicochemical properties and epithelial permeability. J. Drug Target. 2003, 11:61-74.
18. Manford F., Riffo-Vasquez Y., Spina D., Page C.P., Hutt A.J., Moore V., Johansson F., Forbes B. Lack of difference in pulmonary absorption of digoxin, a P-glycoprotein substrate, in mdr1a-deficient and mdr1a-competent mice. J. Pharm. Pharmacol. 2008, 60:1305-1310.
19. Madlova M., Bosquillon C., Asker D., Dolezal P., Forbes B. In-vitro respiratory drug absorption models possess nominal functional P-glycoprotein activity. J. Pharm. Pharmacol. 2009, 61:293-301.
20. Francombe D., Taylor G., Taylor S., Somers G., Edwards C.D., Gumbleton M. Functional role of P-gp efflux in limiting pulmonary drug absorption within an intact lung: application of an isolated perfused rat lung model. Proceedings. Respir. Drug Deliv. 2008, 2008 II:461-464. ISBN 461-930114-930195-930118.
21. Roerig D.L., Audi S.H., Ahlf S.B. Kinetic characterization of P-glycoprotein-mediated efflux of rhodamine 6G in the intact rabbit lung. Drug Metab. Dispos. 2004, 32:953-958.
22. Schinkel A.H., Smit J.J., van Tellingen O., Beijnen J.H., Wagenaar E., van Deemter L., Mol C.A., van der Valk M.A., Robanus-Maandag E.C., te Riele H.P., et al. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994, 77:491-502.
23. Schinkel A.H., Wagenaar E., van Deemter L., Mol C.A., Borst P. Absence of the mdr1a P-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J. Clin. Invest. 1995, 96:1698-1705.
24. Mayer U., Wagenaar E., Beijnen J.H., Smit J.W., Meijer D.K., van Asperen J., Borst P., Schinkel A.H. Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr1a P-glycoprotein. Br. J. Pharmacol. 1996, 119:1038-1044.
25. Schinkel A.H., Wagenaar E., Mol C.A., van Deemter L. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J. Clin. Invest. 1996, 97:2517-2524.
26. van Asperen J., Schinkel A.H., Beijnen J.H., Nooijen W.J., Borst P., van Tellingen O. Altered pharmacokinetics of vinblastine in mdr1a P-glycoprotein-deficient mice. J. Natl Cancer Inst. 1996, 88:994-999.
27. Schinkel A.H., Mayer U., Wagenaar E., Mol C.A., van Deemter L., Smit J.J., van der Valk M.A., Voordouw A.C., Spits H., van Tellingen O., Zijlmans J.M., Fibbe W.E., Borst P. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc. Natl Acad. Sci. USA 1997, 94:4028-4033.
28. van Asperen J., van Tellingen O., Schinkel A.H., Beijnen J.H. Comparative pharmacokinetics of vinblastine after a 96-hour continuous infusion in wild-type mice and mice lacking mdr1a P-glycoprotein. J. Pharmacol. Exp. Ther. 1999, 289:329-333.
29. Troutman M.D., Thakker D.R. Efflux ratio cannot assess P-glycoprotein-mediated attenuation of absorptive transport: asymmetric effect of P-glycoprotein on absorptive and secretory transport across CACO-2 cell monolayers. Pharm. Res. 2003, 20:1200-1209.
30. Troutman M.D., Thakker D.R. Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm. Res. 2003, 20:1210-1224.
31. Ehrhardt C., Kneuer C., Laue M., Schaefer U.F., Kim K.J., Lehr C.M. 16HBE14o- human bronchial epithelial cell layers express P-glycoprotein, lung resistance-related protein, and caveolin-1. Pharm. Res. 2003, 20:545-551.
32. Hamilton K.O., Backstrom G., Yazdanian M.A., Audus K.L. P-glycoprotein efflux pump expression and activity in Calu-3 cells. J. Pharm. Sci. 2001, 90:647-658.
33. Tang F., Horie K., Borchardt R.T. Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa?. Pharm. Res. 2002, 19:765-772.
34. Cavet M.E., West M., Simmons N.L. Transepithelial transport of the fluoroquinolone ciprofloxacin by human airway epithelial Calu-3 cells. Antimicrob. Agents Chemother. 1997, 41:2693-2698.
35. Matsushima S., Maeda K., Kondo C., Hirano M., Sasaki M., Suzuki H., Sugiyama Y. Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein. J. Pharmacol. Exp. Ther. 2005, 314:1059-1067.
36. Takada T., Suzuki H., Sugiyama Y. Characterization of polarized expression of point- or deletion-mutated human BCRP/ABCG2 in LLC-PK1 cells. Pharm. Res. 2005, 22:458-464.
37. Robey R.W., To K.K., Polgar O., Dohse M., Fetsch P., Dean M., Bates S.E. ABCG2: a perspective. Adv. Drug Deliv. Rev. 2009, 61:3-13.
38. Russel F.G., Koenderink J.B., Masereeuw R. Multidrug resistance protein 4 (MRP4/ABCC4): a versatile efflux transporter for drugs and signalling molecules. Trends Pharmacol. Sci. 2008, 29:200-207.
39. Borst P., de Wolf C., van de Wetering K. Multidrug resistance-associated proteins 3, 4, and 5. Pflugers Arch. 2007, 453:661-673.
40. Cole S.P., Deeley R.G. Transport of glutathione and glutathione conjugates by MRP1. Trends Pharmacol. Sci. 2006, 27:438-446.
41. Deeley R.G., Westlake C., Cole S.P. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol. Rev. 2006, 86:849-899.
42. Gradhand U., Kim R.B. Pharmacogenomics of MRP transporters (ABCC1-5) and BCRP (ABCG2). Drug Metab. Rev. 2008, 40:317-354.
43. Flens M.J., Zaman G.J., van der Valk P., Izquierdo M.A., Schroeijers A.B., Scheffer G.L., van der Groep P., de Haas M., Meijer C.J., Scheper R.J. Tissue distribution of the multidrug resistance protein. Am. J. Pathol. 1996, 148:1237-1247.
44. Brechot J.M., Hurbain I., Fajac A., Daty N., Bernaudin J.F. Different pattern of MRP localization in ciliated and basal cells from human bronchial epithelium. J. Histochem. Cytochem. 1998, 46:513-517.
45. Fetsch P.A., Abati A., Litman T., Morisaki K., Honjo Y., Mittal K., Bates S.E. Localization of the ABCG2 mitoxantrone resistance-associated protein in normal tissues. Cancer Lett. 2006, 235:84-92.
46. Torky A.R., Stehfest E., Viehweger K., Taege C., Foth H. Immuno-histochemical detection of MRPs in human lung cells in culture. Toxicology 2005, 207:437-450.
47. Li C.Y., Schuetz J.D., Naren A.P. Tobacco carcinogen NNK transporter MRP2 regulates CFTR function in lung epithelia: implications for lung cancer. Cancer Lett. 2010, 292:246-253.
48. Bandi N., Kompella U.B. Budesonide reduces multidrug resistance-associated protein 1 expression in an airway epithelial cell line (Calu-1). Eur. J. Pharmacol. 2002, 437:9-17.
49. Paturi D.K., Kwatra D., Ananthula H.K., Pal D., Mitra A.K. Identification and functional characterization of breast cancer resistance protein in human bronchial epithelial cells (Calu-3). Int. J. Pharm. 2010, 384:32-38.
50. Koepsell H., Lips K., Volk C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm. Res. 2007, 24:1227-1251.
51. Koepsell H., Schmitt B.M., Gorboulev V. Organic cation transporters. Rev. Physiol. Biochem. Pharmacol. 2003, 150:36-90.
52. Lips K.S., Volk C., Schmitt B.M., Pfeil U., Arndt P., Miska D., Ermert L., Kummer W., Koepsell H. Polyspecific cation transporters mediate luminal release of acetylcholine from bronchial epithelium. Am. J. Respir. Cell Mol. Biol. 2005, 33:79-88.
53. Lips K.S., Luhrmann A., Tschernig T., Stoeger T., Alessandrini F., Grau V., Haberberger R.V., Koepsell H., Pabst R., Kummer W. Down-regulation of the non-neuronal acetylcholine synthesis and release machinery in acute allergic airway inflammation of rat and mouse. Life Sci. 2007, 80:2263-2269.
54. Tamai I., Ohashi R., Nezu J.I., Sai Y., Kobayashi D., Oku A., Shimane M., Tsuji A. Molecular and functional characterization of organic cation/carnitine transporter family in mice. J. Biol. Chem. 2000, 275:40064-40072.
55. Horvath G., Schmid N., Fragoso M.A., Schmid A., Conner G.E., Salathe M., Wanner A. Epithelial organic cation transporters ensure pH-dependent drug absorption in the airway. Am. J. Respir. Cell Mol. Biol. 2007, 36:53-60.
56. Endter S., Francombe D., Ehrhardt C., Gumbleton M. RT-PCR analysis of ABC, SLC and SLCO drug transporters in human lung epithelial cell models. J. Pharm. Pharmacol. 2009, 61:583-591.
57. Kummer W., Wiegand S., Akinci S., Wessler I., Schinkel A.H., Wess J., Koepsell H., Haberberger R.V., Lips K.S. Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse. Respir. Res. 2006, 7:65.
58. Ehrhardt C., Endter S., Tachon G., Gumbleton M. Organic cation transporter expression and activity in human respiratory epithelial cells. Am. J. Crit. Care Med. 2009, 179:A4939.
59. Horvath G., Mendes E.S., Schmid N., Schmid A., Conner G.E., Salathe M., Wanner A. The effect of corticosteroids on the disposal of long-acting beta2-agonists by airway smooth muscle cells. J. Allergy Clin. Immunol. 2007, 120:1103-1109.
60. Glube N., Closs E., Langguth P. OCTN2-mediated carnitine uptake in a newly discovered human proximal tubule cell line (Caki-1). Mol. Pharm. 2007, 4:160-168.
61. Nakamura T., Nakanishi T., Haruta T., Shirasaka Y., Keogh J.P., Tamai I. Transport of ipratropium, an anti-chronic obstructive pulmonary disease (COPD) drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol. Pharm. 2010, 7:187-195.
62. Anzai N., Kanai Y., Endou H. Organic anion transporter family: current knowledge. J. Pharmacol. Sci. 2006, 100:411-426.
63. Hagenbuch B., Meier P.J. The superfamily of organic anion transporting polypeptides. Biochim. Biophys. Acta 2003, 1609:1-18.
64. Hagenbuch B., Meier P.J. Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch. 2004, 447:653-665.
65. Tamai I., Nezu J., Uchino H., Sai Y., Oku A., Shimane M., Tsuji A. Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem. Biophys. Res. Commun. 2000, 273:251-260.
66. Shugarts S., Benet L.Z. The role of transporters in the pharmacokinetics of orally administered drugs. Pharm. Res. 2009, 26:2039-2054.
67. Seki S., Kobayashi M., Itagaki S., Hirano T., Iseki K. Contribution of organic anion transporting polypeptide OATP2B1 to amiodarone accumulation in lung epithelial cells. Biochim. Biophys. Acta 2009, 1788:911-917.
68. Boll M., Herget M., Wagener M., Weber W.M., Markovich D., Biber J., Clauss W., Murer H., Daniel H. Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter. Proc. Natl Acad. Sci. USA 1996, 93:284-289.
69. Doring F., Walter J., Will J., Focking M., Boll M., Amasheh S., Clauss W., Daniel H. Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J. Clin. Invest. 1998, 101:2761-2767.
70. Groneberg D.A., Nickolaus M., Springer J., Doring F., Daniel H., Fischer A. Localization of the peptide transporter PEPT2 in the lung: implications for pulmonary oligopeptide uptake. Am. J. Pathol. 2001, 158:707-714.
71. Lu H., Klaassen C. Tissue distribution and thyroid hormone regulation of Pept1 and Pept2 mRNA in rodents. Peptides 2006, 27:850-857.
72. Saito H., Terada T., Okuda M., Sasaki S., Inui K. Molecular cloning and tissue distribution of rat peptide transporter PEPT2. Biochim. Biophys. Acta 1996, 1280:173-177.
73. Groneberg D.A., Eynott P.R., Doring F., Dinh Q.T., Oates T., Barnes P.J., Chung K.F., Daniel H., Fischer A. Distribution and function of the peptide transporter PEPT2 in normal and cystic fibrosis human lung. Thorax 2002, 57:55-60.
74. Benet L.Z. Predicting drug disposition via application of a Biopharmaceutics Drug Disposition Classification System. Basic Clin. Pharmacol. Toxicol. 2010, 106:162-167.
75. Benet L.Z., Cummins C.L., Wu C.Y. Transporter-enzyme interactions: implications for predicting drug-drug interactions from in vitro data. Curr. Drug Metab. 2003, 4:393-398.
76. Varma M.V., Sateesh K., Panchagnula R. Functional role of P-glycoprotein in limiting intestinal absorption of drugs: contribution of passive permeability to P-glycoprotein mediated efflux transport. Mol. Pharm. 2005, 2:12-21.
77. Fung K.L., Gottesman M.M. A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function. Biochim. Biophys. Acta 2009, 1794:860-871.
78. Kerb R. Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006, 234:4-33.
79. Kalliokoski A., Niemi M. Impact of OATP transporters on pharmacokinetics. Br. J. Pharmacol. 2009, 158:693-705.
80. Maeda K., Sugiyama Y. Impact of genetic polymorphisms of transporters on the pharmacokinetic, pharmacodynamic and toxicological properties of anionic drugs. Drug Metab. Pharmacokinet. 2008, 23:223-235.
81. Schwab M., Eichelbaum M., Fromm M.F. Genetic polymorphisms of the human MDR1 drug transporter. Annu. Rev. Pharmacol. Toxicol. 2003, 43:285-307.
82. Choi M.K., Song I.S. Organic cation transporters and their pharmacokinetic and pharmacodynamic consequences. Drug Metab. Pharmacokinet. 2008, 23:243-253.
83. Siedlinski M., Boezen H.M., Boer J.M., Smit H.A., Postma D.S. ABCC1 polymorphisms contribute to level and decline of lung function in two population-based cohorts. Pharmacogenet. Genomics 2009, 19:675-684.
84. Budulac S.E., Postma D.S., Hiemstra P.S., Kunz L.I., Siedlinski M., Smit H.A., Vonk J.M., Rutgers B., Timens W., Boezen H.M. Multidrug resistance-associated protein-1 (MRP1) genetic variants, MRP1 protein levels and severity of COPD. Respir. Res. 2010, 11:60.
85. Muller P.J., Dally H., Klappenecker C.N., Edler L., Jager B., Gerst M., Spiegelhalder B., Tuengerthal S., Fischer J.R., Drings P., Bartsch H., Risch A. Polymorphisms in ABCG2, ABCC3 and CNT1 genes and their possible impact on chemotherapy outcome of lung cancer patients. Int. J. Cancer 2009, 124:1669-1674.
86. Ishihara Y., Hagiwara K., Zen K., Huqun, Hosokawa Y., Natsuhara A. A case of pulmonary alveolar microlithiasis with an intragenetic deletion in SLC34A2 detected by a genome-wide SNP study. Thorax 2009, 64:365-367.
87. Huqun, Izumi S., Miyazawa H., Ishii K., Uchiyama B., Ishida T., Tanaka S., Tazawa R., Fukuyama S., Tanaka T., Nagai Y., Yokote A., Takahashi H., Fukushima T., Kobayashi K., Chiba H., Nagata M., Sakamoto S., Nakata K., Takebayashi Y., Shimizu Y., Kaneko K., Shimizu M., Kanazawa M., Abe S., Inoue Y., Takenoshita S., Yoshimura K., Kudo K., Tachibana T., Nukiwa T., Hagiwara K. Mutations in the SLC34A2 gene are associated with pulmonary alveolar microlithiasis. Am. J. Respir. Crit. Care Med. 2007, 175:263-268.
88. Rowntree R.K., Harris A. The phenotypic consequences of CFTR mutations. Ann. Hum. Genet. 2003, 67:471-485.
89. van der Deen M., Marks H., Willemse B., Postma D., Müller M., Smit E., Scheffer G., Scheper R., de Vries E., Timens W. Diminished expression of multidrug resistance-associated protein 1 (MRP1) in bronchial epithelium of COPD patients. Virchows Arch. 2006, 449:682-688.
90. van der Deen M., Timens W., Timmer-Bosscha H., van der Strate B.W., Scheper R.J., Postma D.S., de Vries E.G., Kerstjens H.A. Reduced inflammatory response in cigarette smoke exposed Mrp1/Mdr1a/1b deficient mice. Respir. Res. 2007, 8:49.
91. van der Deen M., de Vries E.G., Visserman H., Zandbergen W., Postma D.S., Timens W., Timmer-Bosscha H. Cigarette smoke extract affects functional activity of MRP1 in bronchial epithelial cells. J. Biochem. Mol. Toxicol. 2007, 21:243-251.
92. van der Deen M., Homan S., Timmer-Bosscha H., Scheper R.J., Timens W., Postma D.S., de Vries E.G. Effect of COPD treatments on MRP1-mediated transport in bronchial epithelial cells. Int. J. Chron. Obstruct. Pulm. Dis. 2008, 3:469-475.