2002 Fiscal Year Final Research Report Summary
STUDIES ON THE DEVELOPMENTAL AND SPECIES DIFFERENCE OF CARDIAC FUNCTION: FUNCTIONAL ROLE OF ENDOCARDIAL ENDOTHELIUM AND THE ANALYSIS OF PHYSIOLOGICAL SPECIFICITY OF MOUSE MYOCARDIA
| Project/Area Number |
13670100
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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 |
General pharmacology
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| Research Institution | Toho University |
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Principal Investigator |
SHIGENOBU Koki TOHO UNIVERSITY SCHOOL OF PHARMACEUTICAL SCIENCES, DEPARTMENT OF PHARMACOLOGY, PROFESSOR, 薬学部, 教授 (50012654)
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| Project Period (FY) |
2001 – 2002
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| Keywords | mouse myocardium / endocardial endothelium / prostaglandin / action potential / alpha-adrenergic stimulation / positive inotropism / Na+, Ca2+ exchange |
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| Research Abstract |
Research results are summarized as follows:
1) Since the specific nature of the mouse heart, including negative inotropic response to alpha-adrenergic stimulation, has been found to be closely related to Na+, Ca2+ exchange mechanism (NCX), the selectivity of a newly synthesized compound, SEA0400, was examined in detail. As a result, it was found that SEA0400 selectivity inhibits NCX without affecting Na+ currents, Ca2+ currents, and inwardly rectifying and delayed rectifier K+ currents.
2) Ach produces positive inotropic response in mouse atria through the release of prostaglandins from endocardial endothelium. Since in mouse heart, the specific action potential configuration lacking plateau component minimizes the Ca2+ influx, the negative inotropic component through the activation of IKACh becomes small, and thus the positive inotropic response to endothelium-derived prostaglandins is considered to become marked.
3) Mouse atria showed specific responses to various agents, including 4-aminopyridine, necardipine, or ryanodine, which can be explained by the specific action potential configuration and highly SR-dependent contractile mechanisms in mouse heart.
4) Guinea pig hear gained the specific nature similar to mouse heat by treating with cromakalim, dimethylamiloride, and ouabain, which produces action potential shortening by activating ATP-dependent potassium channels, intracellular alkalization by inhibiting the Na+, H+ exchange, and the increase in intracellular Na+ concentration through the inhibition of Na-pump, respectively.
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Research Products
(4 results)
