Transport of opioids from the brain to the periphery by P-glycoprotein: Peripheral actions of central drugs Journal Article


Authors: King, M.; Su, W.; Chang, A.; Zuckerman, A.; Pasternak, G. W.
Article Title: Transport of opioids from the brain to the periphery by P-glycoprotein: Peripheral actions of central drugs
Abstract: Many peptides and transmitters found within the brain also have peripheral sites of action. We now demonstrate that the brain releases functionally active neurotransmitters/neuromodulators directly from the brain into the blood through a saturable P-glycoprotein (Pgp) transport system. Downregulating Pgp1 expression with antisense reduced the brain-to-blood transport of morphine, β-endorphin and other opioids. Lowering Pgp expression significantly enhanced systemic morphine analgesia and prevented tolerance, but diminished the analgesic activity of centrally administered morphine, implying that supraspinal analgesia resulted from a combination of central and peripheral mechanisms activated by morphine transported from the brain to the blood. Similarly, mice with a disruption of the Mdr1a gene were more sensitive to systemic morphine and less sensitive to morphine given centrally. This ability of the Pgp transport system to pump functionally active compounds from the brain to periphery defines a potentially important mechanism for the central nervous system to modulate peripheral systems.
Keywords: immunohistochemistry; controlled study; nonhuman; mouse; animals; mice; mice, knockout; animal tissue; atp-binding cassette transporters; reverse transcription polymerase chain reaction; animal experiment; down-regulation; neuromodulation; iodine 125; brain; messenger rna; rna, messenger; rat; blood brain barrier; blood-brain barrier; rats; rats, sprague-dawley; morphine; drug sensitivity; drug transport; drug tolerance; biological transport; tail flick test; enkephalin[2,5 dextro penicillamine]; naltrexone; analgesic activity; glycoprotein p; enkephalin, ala(2)-mephe(4)-gly(5)-; beta-endorphin; neurotransmitter; antisense oligonucleotide; enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine]; narcotics; male; priority journal; article; beta endorphin; enkephalin, d-penicillamine (2,5)-; p-glycoproteins
Journal Title: Nature Neuroscience
Volume: 4
Issue: 3
ISSN: 1097-6256
Publisher: Nature Publishing Group  
Date Published: 2001-03-01
Start Page: 268
End Page: 274
Language: English
DOI: 10.1038/85115
PUBMED: 11224543
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 21 May 2015 -- Source: Scopus
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  1. Michael A King
    24 King
  2. Gavril W Pasternak
    414 Pasternak
  3. Albert H Chang
    19 Chang