Transport of prostaglandin E1 across the blood-brain barrier in rats.
The transport of prostaglandin E(1) (PGE(1)) across the blood-brain barrier (BBB) was characterized using an in-situ rat brain perfusion technique. The uptake of [(3)H]PGE(1) was not affected by shortchain monocarboxylic acids (butyric acid and valeric acid). On the other hand, uptake of [(3)H]PGE(1) was significantly inhibited by medium-chain monocarboxylic acids such as hexanoic acid, enanthic acid and octanoic acid. These medium-chain monocarboxylic acids showed a more potent inhibitory effect on [(3)H]PGE(1) uptake with increasing number of carbon atoms. In contrast, there was no decrease in [(3)H]PGE(1) transport by any dicarboxylic acids with 5-8 carbon atoms. Valproic acid decreased [(3)H]PGE(1) uptake, whereas p-aminohippuric acid, a substrate for the organic anion transporter family, did not inhibit [(3)H]PGE(1) transport. Bromocresol green, an inhibitor of prostaglandin transporter (PGT), strongly decreased [(3)H]PGE(1) transport across the BBB. In addition, digoxin and taurocholate, substrates for organic anion transporting polypeptide subtype 2 (Oatp2), significantly inhibited [(3)H]PGE(1) uptake. RT-PCR analysis revealed that PGT mRNA and Oatp2 mRNA are expressed in a capillary-rich fraction from rat brain. Thus, it is suggested that PGE(1) transport across the BBB is mediated by some specific transport systems, possibly by the members of the Oatp family.
Taogoshi
T
T
Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Nomura
A
A
Murakami
T
T
Nagai
J
J
Takano
M
M
D000469:Alkaline Phosphatase / Q000378:metabolism; D000527:Alprostadil / Q000493:pharmacokinetics*; D000818:Animals; D017920:Antiporters / Q000096:biosynthesis; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier; D001961:Bromcresol Green / Q000494:pharmacology; D002196:Capillaries; D002264:Carboxylic Acids / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004077:Digoxin / Q000494:pharmacology; D008297:Male; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis; D010477:Perfusion; D010539:Permeability; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013656:Taurocholic Acid / Q000494:pharmacology
D017920:Antiporters; D002264:Carboxylic Acids; D002316:Cardiotonic Agents; D002756:Cholagogues and Choleretics; D004268:DNA-Binding Proteins; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; C503597:Slco1a4 protein, rat; C451262:Slco1c1 protein, rat; C503528:Slco2a1 protein, rat; D013656:Taurocholic Acid; D004077:Digoxin; D001961:Bromcresol Green; D000469:Alkaline Phosphatase; D000527:Alprostadil