2007 Fiscal Year Final Research Report Summary
Molecular and Functional Characteristics of Glycerol Transporter in HCT-15 Cell Model
| Project/Area Number |
18590149
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
YUASA Hiroaki Nagoya City University, Graduate School of Pharmaceutical Sciences, Professor (20191471)
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| Co-Investigator(Kenkyū-buntansha) |
YAYOI Hayashi Kinjo Gakuin University, College of Pharmacy, Professor (00117847)
KATSUHISA Inoue Nagoya City University, Graduate School of Pharmaceutical Sciences, Associate Professor (50315892)
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| Project Period (FY) |
2006 – 2007
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| Keywords | glycerol / carrier-mediated transport / transporter / Nat-dependent transport / HCT-15 cell / differentiation / competitive inhibition |
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| Research Abstract |
To clarify the molecular and functional characteristics of glycerol transporters, we conducted studies on a Na^+-dependent one in HCT-15 cells, particularly examining the effects on glycerol uptake of 1) cell differentiation induced by butyrate treatment and 2) several compounds structurally analogous to glycerol.
Butyrate treatment brought about an approximately 5-fold increase in the maximum glycerol transport rate, without altering the Michaelis constant (affinity) significantly. Glycerol uptake in butyrate-treated cells was highly Na^+-dependent and specifically inhibited by some structurally analogous compounds as it was in untreated cells, indicating an induction of the Na^+-dependent glycerol transporter. Furthermore, this induction was almost completely suppressed by actinomycin D, an inhibitor of gene transcription, and cycloheximide, an inhibitor of protein synthesis. All these findings provide evidences for the presence of a specific transporter protein for glycerol.
Among sev
… More
eral compounds tested for their inhibitory effects on glycerol uptake, monoacetin and monobutyrin, which are ester type of glycerol derivatives, were found to be the most potent inhibitors. Because they inhibited glycerol uptake competitively, they may possibly be substrates of the glycerol transporter. This would suggest that glycerol ester derivatives of drugs might be delivered via the transporter. Interestingly, enantioselective characteristic was found for competitive inhibition, though relatively weak, by 1, 2-propanediol, where the S-(+)-enantiomer is favored by the transporter than the R-(-)-enantiomer. All these features are also characteristic of transport mediated by a specific transporter protein, providing additional evidences for the presence of such a specific transporter protein for glycerol.
Thus, we could obtain several lines of evidences for the presence of a Na^+-dependent glycerol transporter in HCT-15 cells. This would help in identifying it and elucidating its transport mechanism and physiological role. Less
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