Organic anion-transporting polypeptides mediate transport of opioid peptides across blood-brain barrier.

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Gao B, Hagenbuch B, Kullak-Ublick GA, Benke D, Aguzzi A, Meier PJ

Organic anion-transporting polypeptides mediate transport of opioid peptides across blood-brain barrier.

J Pharmacol Exp Ther. 2000 Jul;294(1):73-9.

PubMed ID

10871297 [ View in PubMed

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Abstract

Organic anion-transporting polypeptides (Oatps) are a rapidly growing gene family of polyspecific membrane transporters. In rat brain, Oatp1 (gene symbol Slc21a1) and Oatp2 (Slc21a5) are localized at the apical and basolateral domains, respectively, of the choroid plexus epithelium. Furthermore, Oatp2 is strongly expressed at the rat blood-brain barrier (BBB). This study localizes the human OATP (now called OATP-A; SLC21A3) at the BBB in humans. Furthermore, with the Xenopus laevis oocyte system the delta-opioid receptor agonists [D-penicillamine(2,5)]enkephalin (DPDPE) and deltorphin II were identified as new transport substrates of OATP-A. This OATP-A-mediated DPDPE and deltorphin II transport exhibited apparent K(m) values of approximately 202 and 330 microM, respectively, and OATP-A-mediated deltorphin II transport was inhibited by the mu-opioid receptor agonist Tyr-D-Ala-Gly-N-methyl-Phe-glycinol, the endogenous peptide Leu-enkephalin, and the opiate antagonists naloxone and naltrindole. DPDPE also was transported by rat Oatp1 (K(m) approximately 48 microM) and Oatp2 (K(m) approximately 19 microM), whereas deltorphin II was only transported by Oatp1 (K(m) approximately 137 microM). These results demonstrate that OATP-A can mediate transport of the analgesic opioid peptides DPDPE and deltorphin II across the human BBB. Furthermore, because rat Oatp1 and Oatp2 exhibit similar but not identical transport activities as OATP-A, the results generally indicate that members of the Oatp/OATP gene family of membrane transporters play an important role in carrier-mediated transport of opioid peptides across the BBB and blood-cerebrospinal fluid barrier of the mammalian brain.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Conjugated estrogens	Solute carrier organic anion transporter family member 1A2	Protein	Humans	Unknown	Substrate Inhibitor	Details
Naloxone	Solute carrier organic anion transporter family member 1A2	Protein	Humans	Unknown	Inhibitor	Details