title: Mechanism of nucleoside uptake in rat placenta and induction of placental CNT2 in experimental diabetes.
abstract: The purpose of this study was to clarify the transport characteristics of nucleosides in rat placenta and the changes of functional expression of nucleoside transporters in rat placenta with experimental diabetes mellitus. Placental uptake clearances of [(3)H]adenosine and [(3)H]zidovudine from maternal blood was much higher than that of [(14)C]mannitol. Xenopus oocytes injected with rat ENT1 and ENT2 cRNA took up [(3)H]adenosine with K(m) values of 6.1 and 26 µM, respectively. [(3)H]Adenosine transport by rat placental brush-border membrane vesicles (BBMV) was saturable and was inhibited by nitrobenzylthioinosine (NBMPR), a specific ENT inhibitor, in a manner consistent with involvement of both rat ENT1 and ENT2. [(3)H]Didanosine was modestly taken up by placenta, and the inhibitory effect of 100 µM NBMPR on [(3)H]ddI uptake by BBMV suggested a role of ENT2-mediated transport. Expression of ENT1, ENT2, ENT3, CNT2, and CNT3 mRNAs was detected in placenta of control and streptozotocin (STZ)-induced diabetic pregnant rats, and CNT2 (SLC28A2) expression was significantly increased in STZ-induced diabetic rats. Consistently, Na(+)-dependent adenosine uptake by BBMV from STZ-induced diabetic pregnant rats was higher than that from control rats. These results suggest the involvement of placental ENT2 as well as ENT1 in nucleoside uptake from maternal blood, and the induction of CNT2 in experimental diabetes mellitus.
authors.affiliation: Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishimura
authors.forename: Takuya
authors.initials: T
authors.lastname: Chishu
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tomi
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakamura
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sato
authors.forename: Noriko
authors.initials: N
authors.lastname: Kose
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Sai
authors.forename: Emi
authors.initials: E
authors.lastname: Nakashima
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D016640:Diabetes, Gestational / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D008431:Maternal-Fetal Exchange; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D009705:Nucleosides / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D009865:Oocytes; D010920:Placenta / Q000378:metabolism* / Q000648:ultrastructure; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014327:Trophoblasts / Q000378:metabolism / Q000648:ultrastructure; D015854:Up-Regulation; D014982:Xenopus laevis; D015215:Zidovudine / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2; D026901:Membrane Transport Proteins; D009705:Nucleosides; D012333:RNA, Messenger; C438652:Slc29a1 protein, rat; C438655:Slc29a2 protein, rat; C065171:cif nucleoside transporter; D013868:Thioinosine; D015215:Zidovudine; C001789:4-nitrobenzylthioinosine; D000241:Adenosine