The multidrug transporters - Proteins of an ancient immune system

B. Sarkadi, M. Müller, Zsolt Holló

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The multidrug resistance proteins, discovered as membrane transporters producing chemotherapy-resistance in cancer, are functioning as complex cellular defence systems through recognition and energy-dependent removal of a large variety of toxic agents. The multidrug transporters belong to the ATP-binding cassette (ABC) transporters, present both in prokaryotes and eukaryotes and built from a combination of characteristic membrane-spanning helices and cytoplasmic ATP-binding domains. In mammals the MDR1 (P-glycoprotein) extrudes large hydrophobic compounds and provides the basis of the blood-brain and the blood-testis barrier for such molecules. The multidrug resistance-associated protein (MRP) and its homologues have a major role in the cellular export of large organic anions, including e.g. conjugated bile salts and glutathione-conjugates. The substrate recognition, that is the self and non-self discrimination and the ATP-dependent foreign agent extrusion are directly coupled within the structure of these large plasma membrane proteins. Here we suggest that the multidrug transporters are essential parts of our immune-defence system, working as 'cellular antitoxic' mechanisms.

Original languageEnglish
Pages (from-to)215-219
Number of pages5
JournalImmunology Letters
Volume54
Issue number2-3
DOIs
Publication statusPublished - Dec 2 1996

Fingerprint

Immune System
Blood-Testis Barrier
Adenosine Triphosphate
P-Glycoproteins
Multidrug Resistance-Associated Proteins
ATP-Binding Cassette Transporters
Membrane Transport Proteins
Poisons
P-Glycoprotein
Eukaryota
Blood-Brain Barrier
Bile Acids and Salts
Anions
Glutathione
Blood Proteins
Mammals
Membrane Proteins
Proteins
Cell Membrane
Drug Therapy

Keywords

  • cellular immune defense
  • MDR1
  • MRP
  • multidrug transporter

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

The multidrug transporters - Proteins of an ancient immune system. / Sarkadi, B.; Müller, M.; Holló, Zsolt.

In: Immunology Letters, Vol. 54, No. 2-3, 02.12.1996, p. 215-219.

Research output: Contribution to journalArticle

@article{ba628059d43340ff8a79e51db669e36c,
title = "The multidrug transporters - Proteins of an ancient immune system",
abstract = "The multidrug resistance proteins, discovered as membrane transporters producing chemotherapy-resistance in cancer, are functioning as complex cellular defence systems through recognition and energy-dependent removal of a large variety of toxic agents. The multidrug transporters belong to the ATP-binding cassette (ABC) transporters, present both in prokaryotes and eukaryotes and built from a combination of characteristic membrane-spanning helices and cytoplasmic ATP-binding domains. In mammals the MDR1 (P-glycoprotein) extrudes large hydrophobic compounds and provides the basis of the blood-brain and the blood-testis barrier for such molecules. The multidrug resistance-associated protein (MRP) and its homologues have a major role in the cellular export of large organic anions, including e.g. conjugated bile salts and glutathione-conjugates. The substrate recognition, that is the self and non-self discrimination and the ATP-dependent foreign agent extrusion are directly coupled within the structure of these large plasma membrane proteins. Here we suggest that the multidrug transporters are essential parts of our immune-defence system, working as 'cellular antitoxic' mechanisms.",
keywords = "cellular immune defense, MDR1, MRP, multidrug transporter",
author = "B. Sarkadi and M. M{\"u}ller and Zsolt Holl{\'o}",
year = "1996",
month = "12",
day = "2",
doi = "10.1016/S0165-2478(96)02676-4",
language = "English",
volume = "54",
pages = "215--219",
journal = "Immunology Letters",
issn = "0165-2478",
publisher = "Elsevier",
number = "2-3",

}

TY - JOUR

T1 - The multidrug transporters - Proteins of an ancient immune system

AU - Sarkadi, B.

AU - Müller, M.

AU - Holló, Zsolt

PY - 1996/12/2

Y1 - 1996/12/2

N2 - The multidrug resistance proteins, discovered as membrane transporters producing chemotherapy-resistance in cancer, are functioning as complex cellular defence systems through recognition and energy-dependent removal of a large variety of toxic agents. The multidrug transporters belong to the ATP-binding cassette (ABC) transporters, present both in prokaryotes and eukaryotes and built from a combination of characteristic membrane-spanning helices and cytoplasmic ATP-binding domains. In mammals the MDR1 (P-glycoprotein) extrudes large hydrophobic compounds and provides the basis of the blood-brain and the blood-testis barrier for such molecules. The multidrug resistance-associated protein (MRP) and its homologues have a major role in the cellular export of large organic anions, including e.g. conjugated bile salts and glutathione-conjugates. The substrate recognition, that is the self and non-self discrimination and the ATP-dependent foreign agent extrusion are directly coupled within the structure of these large plasma membrane proteins. Here we suggest that the multidrug transporters are essential parts of our immune-defence system, working as 'cellular antitoxic' mechanisms.

AB - The multidrug resistance proteins, discovered as membrane transporters producing chemotherapy-resistance in cancer, are functioning as complex cellular defence systems through recognition and energy-dependent removal of a large variety of toxic agents. The multidrug transporters belong to the ATP-binding cassette (ABC) transporters, present both in prokaryotes and eukaryotes and built from a combination of characteristic membrane-spanning helices and cytoplasmic ATP-binding domains. In mammals the MDR1 (P-glycoprotein) extrudes large hydrophobic compounds and provides the basis of the blood-brain and the blood-testis barrier for such molecules. The multidrug resistance-associated protein (MRP) and its homologues have a major role in the cellular export of large organic anions, including e.g. conjugated bile salts and glutathione-conjugates. The substrate recognition, that is the self and non-self discrimination and the ATP-dependent foreign agent extrusion are directly coupled within the structure of these large plasma membrane proteins. Here we suggest that the multidrug transporters are essential parts of our immune-defence system, working as 'cellular antitoxic' mechanisms.

KW - cellular immune defense

KW - MDR1

KW - MRP

KW - multidrug transporter

UR - http://www.scopus.com/inward/record.url?scp=0030566751&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030566751&partnerID=8YFLogxK

U2 - 10.1016/S0165-2478(96)02676-4

DO - 10.1016/S0165-2478(96)02676-4

M3 - Article

C2 - 9052881

AN - SCOPUS:0030566751

VL - 54

SP - 215

EP - 219

JO - Immunology Letters

JF - Immunology Letters

SN - 0165-2478

IS - 2-3

ER -