Elsevier

Neuroscience Letters

Volume 301, Issue 3, 6 April 2001, Pages 155-158
Neuroscience Letters

Uptake and efflux of the peptidic delta-opioid receptor agonist [D-penicillamine2,5]-enkephalin at the murine blood–brain barrier by in situ perfusion

https://doi.org/10.1016/S0304-3940(01)01640-8Get rights and content

Abstract

P-glycoprotein (P-gp) and organic anion transporting polypeptides (Oatp) are expressed at the blood–brain barrier (BBB). There is little functional evidence for Oatp-mediated transport at the BBB. The peptidic delta opioid-receptor agonist [D-penicillamine2,5]-enkephalin (DPDPE) is a substrate of mdr1a P-gp and Oatp2. The present study evaluated the influence of these transporters on brain uptake of DPDPE by in situ perfusion in mice. Brain uptake was increased ~12-fold in mice lacking P-gp in the BBB, but the P-gp inhibitor dexverapamil did not increase uptake in P-gp-competent mice. In P-gp-deficient mice, DPDPE uptake was saturable (Km ~24 mM), and was inhibited by dexverapamil and the Oatp2 substrates digoxin, estradiol-17β-glucuronide and fexofenadine. These results confirm P-gp-mediated efflux of DPDPE, and suggest functional uptake transport of DPDPE by Oatp, at the murine BBB.

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