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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Passage of a delta-opioid receptor selective enkephalin, [D-penicillamine2,5] enkephalin, across the blood-brain and the blood-cerebrospinal fluid barriers.

[D-Penicillamine2,5] enkephalin (DPDPE) is an enzymatically stable, delta-opioid receptor-selective peptide, which produces analgesia when given intracerebroventricularly. However, because only modest analgesic effects were seen after subcutaneous administration of DPDPE, it has been inferred that it does not cross the blood-brain barrier well. In this present study, a vascular brain perfusion technique in anesthetized rats was used to measure directly whether [3H]DPDPE could cross the blood-brain and/or the blood-CSF barriers. The results indicated that the brain uptake of [3H]DPDPE was significantly greater than that of [14C]sucrose, a vascular marker (p < 0.01), and than that of [3H]DPDPE into the CSF (p < 0.01). Furthermore, HPLC analysis confirmed the integrity of the 3H to DPDPE and demonstrated that intact [3H]DPDPE entered the brain. Although 1 mM leucine-enkephalin failed to inhibit uptake of [3H]DPDPE, unlabeled DPDPE (100 microM) caused a significant inhibition of the brain uptake (p < 0.01) but not the CSF uptake of [3H]DPDPE. These data provide evidence that intact [3H]DPDPE enters the CNS of anesthetized rats by saturable and nonsaturable mechanisms. In addition, the saturable mechanism is likely to be found at the blood-brain barrier, with the blood-CSF barrier playing only a minor role in the brain uptake of this peptide.[1]

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