Blood-brain barrier active efflux transporters: ATP-binding cassette gene family.
The blood-brain barrier (BBB) contributes to brain homeostasis by protecting the brain from potentially harmful endogenous and exogenous substances. BBB active drug efflux transporters of the ATP-binding cassette (ABC) gene family are increasingly recognized as important determinants of drug distribution to, and elimination from, the CNS. The ABC efflux transporter P-glycoprotein (Pgp) has been demonstrated as a key element of the BBB that can actively transport a huge variety of lipophilic drugs out of the brain capillary endothelial cells that form the BBB. In addition to Pgp, other ABC efflux transporters such as members of the multidrug resistance protein (MRP) family and breast cancer resistance protein (BCRP) seem to contribute to BBB function. Consequences of ABC efflux transporters in the BBB include minimizing or avoiding neurotoxic adverse effects of drugs that otherwise would penetrate into the brain. However, ABC efflux transporters may also limit the central distribution of drugs that are beneficial to treat CNS diseases. Furthermore, neurological disorders such as epilepsy may be associated with overexpression of ABC efflux transporters at the BBB, resulting in pharmacoresistance to therapeutic medication. Therefore, modulation of ABC efflux transporters at the BBB forms a novel strategy to enhance the penetration of drugs into the brain and may yield new therapeutic options for drug-resistant CNS diseases.
Löscher
Wolfgang
W
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover D-30559, Germany. wolfgang.loescher@tiho-hannover.de
Potschka
Heidrun
H
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans
D018528:ATP-Binding Cassette Transporters
Biochim Biophys Acta. 1999 Dec 6;1461(2):347-57
10581366
Novartis Found Symp. 2002;243:19-31; discussion 31-7, 180-5
11990777
J Histochem Cytochem. 1989 Feb;37(2):159-64
2463300
Brain. 2002 Jan;125(Pt 1):22-31
11834590
Trends Pharmacol Sci. 2002 Mar;23(3):113-8
11879677
Int J Clin Pharmacol Ther. 1998 Jan;36(1):50-4
9476149
Top HIV Med. 2003 Jul-Aug;11(4):136-9
12876331
Adv Drug Deliv Rev. 2002 Mar 31;54(3):315-28
11922950
Br J Hosp Med. 1991 Jan;45(1):32-4
2009437
Epilepsy Behav. 2003 Dec;4 Suppl 4:S26-30
14654425
Curr Pharm Des. 2004;10(12):1313-24
15134483
Proc Natl Acad Sci U S A. 1989 Jan;86(2):695-8
2563168
Curr Drug Targets. 2003 May;4(4):297-304
12699350
Mol Microbiol. 2002 Jun;44(5):1123-30
12068801
Neuroscience. 2004;123(3):751-9
14706787
Biochem Pharmacol. 2004 Jan 15;67(2):269-76
14698039
J Pharmacol Exp Ther. 2003 Jul;306(1):124-31
12663688
Psychiatr Clin North Am. 1998 Jun;21(2):293-307
9670227
Pharmacol Rev. 2001 Dec;53(4):569-96
11734619
Mol Pharmacol. 2000 Dec;58(6):1357-67
11093774
Curr Opin Neurol. 2003 Apr;16(2):197-201
12644749
J Pharmacol Exp Ther. 2002 Aug;302(2):407-15
12130697
Leuk Lymphoma. 2002 Jun;43(6):1221-8
12152989
Adv Drug Deliv Rev. 1999 Apr 5;36(2-3):179-194
10837715
Anesthesiology. 2000 May;92(5):1392-9
10781286
Pharmacology. 2004 Apr;70(4):169-76
15001817
Neuropsychopharmacology. 2000 Apr;22(4):380-7
10700657
Adv Drug Deliv Rev. 2003 Jan 21;55(1):83-105
12535575
Neuroreport. 1999 Nov 8;10(16):3437-41
10599858
Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2470-5
14983033
Curr Drug Metab. 2004 Feb;5(1):95-108
14965253
Pharm Biotechnol. 1999;12:353-86
10742982
Br J Pharmacol. 1999 Oct;128(3):563-8
10516633
Novartis Found Symp. 2002;243:38-47; discussion 47-53, 180-5
11990780
Novartis Found Symp. 2002;243:149-59; discussion 159-66, 180-5
11990774
Psychiatr Clin North Am. 1996 Jun;19(2):179-200
8827185
N Engl J Med. 2003 Apr 10;348(15):1442-8
12686700
Epilepsia. 2003 Nov;44(11):1388-96
14636345
Epilepsia. 2004 May;45(5):441-51
15101825
Nat Med. 2004 Jul;10(7):685-92
15229516
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3900-5
10097135
Int J Clin Pharmacol Ther. 2000 Mar;38(3):111-21
10739114
Vascul Pharmacol. 2002 Jun;38(6):339-48
12529928
Epilepsia. 2003 Dec;44(12):1479-86
14636316
Cancer Control. 2003 Mar-Apr;10(2):159-65
12712010
Drug Metab Dispos. 2003 Nov;31(11):1337-45
14570765
Cancer Res. 2004 May 1;64(9):3296-301
15126373
Drugs Today (Barc). 2004 Jan;40(1):5-22
14988766
Oncogene. 2003 Oct 20;22(47):7340-58
14576842
Neuroreport. 2002 Nov 15;13(16):2059-63
12438926
J Clin Invest. 1998 Jan 15;101(2):289-94
9435299
Pediatr Neurol. 1999 Oct;21(4):731-4
10580886
Cell Mol Life Sci. 2001 Jun;58(7):931-59
11497241
J Clin Psychiatry. 1999;60 Suppl 23:14-9
10625195
Int J Clin Pharmacol Ther. 2000 Feb;38(2):69-74
10706193
J Histochem Cytochem. 2005 Apr;53(4):517-31
15805426
Epilepsy Res. 2004 Feb;58(2-3):85-91
15120740
J Pharmacol Exp Ther. 2002 Apr;301(1):7-14
11907151
Neuroreport. 2001 Nov 16;12(16):3557-60
11733711
Pharmacogenomics. 2001 Feb;2(1):51-64
11258197
Curr Drug Metab. 2004 Feb;5(1):21-53
14965249
Epilepsia. 1995 Jan;36(1):1-6
8001500
Hepatology. 1998 Feb;27(2):537-45
9462655
Brain Res. 2000 Sep 8;876(1-2):148-53
10973603
Cell Mol Life Sci. 2004 Mar;61(6):682-99
15052411
Brain Res. 1999 Feb 20;819(1-2):143-6
10082869
J Neurosci Res. 2000 Jun 1;60(5):594-601
10820430
Biol Psychiatry. 2003 Oct 15;54(8):840-6
14550684
Nat Neurosci. 2001 Mar;4(3):268-74
11224543
Biochem Biophys Res Commun. 2001 Jun 22;284(4):863-9
11409873
Food Chem Toxicol. 2004 Jun;42(6):995-1002
15110109
J Pharmacol Exp Ther. 2003 Apr;305(1):197-204
12649369
Epilepsy Res. 2002 Oct;51(3):257-68
12399076
J Clin Invest. 2002 Nov;110(9):1309-18
12417570
Eur J Clin Invest. 2003 Nov;33 Suppl 2:6-9
14641550
Anaesth Intensive Care. 2002 Apr;30(2):183-91
12002926
J Natl Cancer Inst. 2000 Aug 16;92(16):1295-302
10944550
Epilepsia. 2001 Dec;42(12):1501-6
11879359
AIDS. 2001 Mar 9;15(4):483-91
11242145
Biochem J. 2003 Dec 1;376(Pt 2):313-38
13678421
Neuroreport. 2004 Jul 19;15(10):1657-61
15232302
Novartis Found Symp. 2002;243:83-96; discussion 96-102, 180-5
11990784
Drug Metab Dispos. 2000 Sep;28(9):1058-62
10950849
J Neurochem. 1997 Mar;68(3):1278-85
9048775
J Pharm Sci. 2003 Sep;92(9):1739-53
12949994
J Neurochem. 2002 Aug;82(3):716-9
12153495
Scand J Rheumatol. 2003;32(6):325-36
15080263
Cancer Treat Rev. 2000 Dec;26(6):449-62
11139374
Biochim Biophys Acta. 1976 Nov 11;455(1):152-62
990323
Ann Neurol. 2003 Apr;53(4):469-79
12666114
Psychoneuroendocrinology. 2004 May;29(4):423-47
14749091
Curr Pharm Des. 2004;10(12):1295-312
15134482
Epilepsy Res. 2004 Jan;58(1):67-79
15066676
Neuroscience. 2003;118(2):417-29
12699778
Neuroreport. 2001 Aug 8;12(11):2387-9
11496115
Epilepsy Res. 1999 Apr;34(2-3):109-22
10210025
Int J Neuropsychopharmacol. 2004 Sep;7(3):341-9
15003146
Pharm Res. 2000 Jun;17(6):749-53
10955852
Eur J Pharmacol. 2002 Sep 13;451(2):149-55
12231384
J Neurosci. 2002 Jul 15;22(14):5833-9
12122045
Neuroreport. 2003 Nov 14;14(16):2041-6
14600494
Adv Drug Deliv Rev. 2000 Dec 15;45(2-3):295-307
11108981
Cell Mol Neurobiol. 2000 Apr;20(2):165-81
10696508
Antimicrob Agents Chemother. 2002 Jul;46(7):2284-6
12069991
Drug Metab Dispos. 1999 Jul;27(7):827-34
10383928
Drug Metab Dispos. 1999 Aug;27(8):937-41
10421622
Brain Res. 2003 May 9;971(2):221-31
12706238
Exp Brain Res. 1999 Jun;126(4):509-16
10422714
J Drug Target. 2002 Feb;10(1):73-9
11996089
J Clin Invest. 2000 Feb;105(3):279-85
10675353
Lancet. 2001 Jan 6;357(9249):42-3
11197364
Adv Drug Deliv Rev. 2003 Jan 21;55(1):3-29
12535572
J Neurovirol. 1999 Dec;5(6):556-69
10602397
N Engl J Med. 2000 Feb 3;342(5):314-9
10660394