Organic Anion-Transporting Polypeptides Mediate Transport of Opioid Peptides across Blood-Brain Barrier

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