| Project/Area Number |
16590116
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | Nagoya City University |
|---|
Principal Investigator |
YUASA Hiroaki Nagoya City University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (20191471)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Yayoi Nagoya City University, Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究科, 講師 (00117847)
INOUE Katsuhisa Nagoya City University, Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究科, 講師 (50315892)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | glycerol / carrier-mediated transport / transporter / Na^+-dependent transport / rat / intestine / HCT-15 cell / polyol / HCT-15細胞 / 吸収 / アルコール / クロラムフェニコール |
|---|
| Research Abstract |
The uptake of glycerol in the everted sacs of the rat small intestine was highly saturable, suggesting the involvement of carrier-mediated transport. Although moderate passive transport component was also observed, it was found that carrier-mediated transport is prevailing at concentrations far lower than the Michaelis constant, where carrier-mediated transport is in the linear phase and most efficient. The glycerol carrier was further suggested to be of Na^+-dependent and secondary active, and specific to glycerol and some analogous compounds. It should also be noted that carrier-mediated glycerol transport is highly efficient, being comparable to D-glucose transport by SGLT1(sodium-dependent glucose transporter 1), which is well known for its very high efficiency. These characteristics of carrier-mediated glycerol transport were consistent with those in the closed loop and the perfused segment of the rat small intestine in situ. Thus, we successfully demonstrated the presence of a carrier-mediated transport system specific to glycerol and some analogous compounds in the rat intestinal tissue, and characterized it kinetically.
HCT-15 is a human colon cancer cell line, which was found to be able to perform Na^+-dependent glycerol uptake in the present research project. Although the glycerol carrier in HCT-15 cells was suggested to be different from the one in the small intestine as there was a 50-fold difference in the Michaelis constants, the profiles of inhibition of glycerol transport by various compounds were quite similar, indicating similar characteristics in recognition of substrates and/or inhibitors. Therefore, it maybe possible to use HCT-15 cells for screening inhibitors and potential substrates. HCT-15 could still be a useful model cell line for studies to identify a group of Na^+-dependent glycerol carriers and to elucidate their transport mechanism. Such carriers would be of interest as possible pathways of drug delivery and targets of drug development.
|
