Mechanisms of suppression of insulin signaling by Na channel blockers
| Project/Area Number |
15590040
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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 |
Physical pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KURODA Yoshihiro Kyoto University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (90093236)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | local anesthetics / lidocaine / oligopeptide / KIFMK / KIYEK / insulin receptor / suppression of phosphorylation / dephosphorylation |
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| Research Abstract |
1)Suppression of autophosphorylation of insulin receptor(IR) by local anesthetic lidocaine and various oligopeptides
The 40 mM of lidocaine and the 4 mM of oligopeptides, KIFMK and KIYEK, suppressed autophosphorylation of IR below 20% or more. DIYET and KIQMK, suppressed autophosphorylation less effectively than did KIFMK and KIYEK.
2)Dephosphorylation of pre-phosphorylated IR by lidocaine and various oligopeptides
The 40 mM of lidocaine and 4 mM of KIYEK and DIYET decreased phosphorylation of pre-phosphorylated IR to 35 and 30%, respectively. In contrast, KIFMK showed no dephosphorylation effect.
3)Interactions between activation loop peptide(AL) of IR and lidocaine or oligopeptides by fluorescence spectra
Lidocaine, KIYEK, and DIYET, which had dephosphorylation effects on activated IR, reduced fluorescence intensities of AL due to 280 nm excitation and 303 nm emission. In contrast, KIFMK, which showed no dephosphorylation effect, increased the intensities. LPFFD had no effect on the intensities.
4)Dephosphorylation effects for IR by lidocaine and oligopeptides as studied by surface plasmon resonance(SPR) experiments
After various SPR experiments performed by varying ligands to be immobilized and analytes to be flowed with running buffer, it was concluded that the SPR method is inadequate for analyzing phosphorylation of IR.
5)Suppression of autophosphorylation of epidermal growth factor receptor(EGFR) by oligopeptides
Suppression effects of oligopeptides, the amino acid sequences of which followed those of autophosphorylation sites of EGFR, on autophosphorylation of EGFR were studied. The oligopeptides which followed the amino acid sequences around Y1148 and Y1173 were found to effectively suppress autophoshorylation of EGFR.
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Report
(3 results)
Research Products
(4 results)
