| Project/Area Number |
16590104
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | HOKKAIDO UNIVERSITY |
|---|
Principal Investigator |
SUGAWARA Mitsuru Hokkaido Univ., Hokkaido Univ.Hospital, Asso.Prof., 病院, 助教授 (60332467)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ISEKI Ken Hokkaido Univ., Grad School of Pharm., Prof., 大学院・薬学研究科, 教授 (40203062)
HIRANO Takeshi Hokkaido Univ., Grad School of Pharm., Instructor, 大学院・薬学研究科, 講師 (00322826)
宮崎 勝巳 北海道大学, 病院・教授 (30166144)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
|
|---|
| Keywords | nucleoside transporter / placental permeation / ribavirin |
|---|
| Research Abstract |
Ribavirin, an antivirus agent, was shown to be transported via CNT3 and ENT1 in human choriocarcinoma (Bewo) cells. Then we investigated characteristics of each subtype of the nucleoside transporters. Using Xenopus laevis oocytes expressing human nucleoside transporters, it was suggested that ribavirin has relatively higher affinity (〜20 μM) to sodium-dependent transporters (CNT) and lower affinity (〜mM) to sodium-independent transporters (ENT). Since it is reported that both CNT and ENT express in the brush border membrane of the placental epithelial cells, we measured the uptake of rebavirin by the oocytes expressing both hCNT3 and hENT1 (co-expressing oocyte). The uptake of ribavirin by co-expressing oocytes was lower than that by the oocytes that expressing only hCNT3. These results suggest that the concentration of ribavirin in the cells is maintained by the uptake via CNT and efflux via ENT and permeation of ribavirin through the placenta is not concentrative toward fetal side.
On the other hand, it was suggested that in the intestine, in which CNT and ENT express in brush border membrane and basolateral membrane, respectively, these transporters also contribute to the absorption of ribavirin. In the intestine, rebavirin was suggested to be taken up by concentrative manner through the brush border membrane, and then fluxed into blood flow by facilitated diffusion through the basolateral membrane.
|
