Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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, beta-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.
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PMID:Transport of opioids from the brain to the periphery by P-glycoprotein: peripheral actions of central drugs. 1122 31