2014 Fiscal Year Annual Research Report
細動脈での利尿剤スピロノラクトンの情報伝達機構の解明：受容体はどこに存在するか？
| Project/Area Number |
24590259
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| Research Institution | Iwate Medical University |
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Principal Investigator |
齋野 朝幸 岩手医科大学, 医学部, 教授 (40305991)
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| Co-Investigator(Kenkyū-buntansha) |
松浦 誠 岩手医科大学, 薬学部, 講師 (00405846)
佐藤 洋一 岩手医科大学, 医学部, 教授 (40118253)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | spironolactone / Ca2+ ion / arteriole / Ca2+ imaging / confocal microscopy |
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| Outline of Annual Research Achievements |
We reported previously that spironolactone (SPL) induced an increase in intracellular Ca2+ concentration ([Ca2+]i) in rat testicular arteriole smooth muscle cells. In the present study, we further investigated the mechanism of SPL-induced [Ca2+]i dynamics in rat arteriole smooth muscles. The increase in [Ca2+]i induced by SPL was markedly inhibited in extracellular Ca2+-free conditions and in the presence of diltiazem or gadolinium. In contrast, the phospholipase C inhibitor (U73122), did not affect the SPL-induced increase in [Ca2+]i, similar to what was observed for 2-APB(an inhibitor of IP3-dependent Ca2+ mobilization). Moreover, the protein kinase A (PKA) inhibitor H89 partially inhibited the SPL-induced increase in [Ca2+]i, whereas the protein kinase C (PKC) inhibitor GF109203X did not. Either suramin (a non-specific G protein antagonist) or NF449 (an inhibitor of the α-subunit of the stimulatory G protein Gsα), partially blocked the SPL-induced increase in [Ca2+]i Similarily, either mifepristone, a glucocorticoid-receptor antagonist, or flutamide, a non-steroidal antiandrogen drug, partially blocked the SPL-induced increase in [Ca2+]i. We suggest that the SPL-induced increase in [Ca2+]i in arterioles is mediated both by Ca2+ influx from the extracellular fluid and by Ca2+ mobilization from internal Ca2+ stores, with the former being dominant. We thus propose that SPL interacts with both extracellular and intracellular receptors in rat testicular arterioles, which is followed by an increase in intracellular Ca2+ that causes smooth-muscle contraction.
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