Spontaneous relaxation of isolated smooth muscle cells shortened with muscarinic receptor stimulation
| Project/Area Number |
07457544
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | MEIJI COLLEGE OF PHARMACY |
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Principal Investigator |
UCHIDA Masaatsu MEIJI COLLEGE OF PHARMACY FACULTY OF PHARMACY PROFESSOR, 薬学部, 教授 (90097197)
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| Co-Investigator(Kenkyū-buntansha) |
OISHI Kazuhiko MEIJI COLLEGE OF PHARMACY FACULTY OF PHARMACY RESEARCH ASSOCIATE, 薬学部, 助手 (80203701)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | relaxation / protein kinase C / guinea-pig stomach / smooth muscle cells / streptolysin-O / permeabilize / acetylcholine / actin / 自然弛緩 / 収縮 / ムスカリ受容体 / 平滑筋 / 培養細胞 / 分化 / ムスカリン受容体 / 張力 / カルシウムイオン / 膜透過性 |
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| Research Abstract |
Contracted smooth muscle relaxs spontaneously when contractile agonist is removed. In this study, we have provide first evidence that muscarinic receptor-mediated activation of PKC in the process of ACh-induced cell shortening is necessary for the subsequent relaxation of the shortened cells. This study was done with streptolysin-O-permeabilized single smooth muscle cells by measuring cell shortening under the condition without any tension load.
PKC-dependent relaxation mechanism was found to be specific for the contractile stimulation of muscarinic receptors. Moreover, the receptor-mediated activation of PKC in the process of ACh-induced cell shortening was required for the subsequent relaxation of the shortened cells. Thus, it is likely that PKC-dependent promotion stage is required for the subsequent relaxation which is triggered by removal of contractile stimulant ACh and fall of free Ca^<2+>. In contrast, the relaxation from Ca^<2+>-induced cell shortening was independent on PKC.Th
… More
e differences in PKC-dependence could be due to the activation of muscarinic receptor-mediated metabotropic signaling.
It is unclear what is the mechanism underlying PKC-dependent promotion of relaxation. It is, however, most likely that PKC-dependent activation of regulatory mechanisms during agonist-induced contractions could be involved. Several possible regulatory mechanisms which are related to maintenance of tone and latch state are reported to be activated PKC-dependently. We focused one of these mechanisms, the reorganization of cytoskeleton. We have obtained several evidences that PKC regulation of actin cytoskeletal reorganization during contraction is responsible for subsequent relaxation from agonist-induced contraction.
Contracted smooth muscle tissues under the condition with tension-load were readily relaxd by a wash even if the contraction was induced by ACh in the presence of a protein kinase inhibitor. These results arise the possibility that the PKC-dependent relaxation mechanism, which actively participates in the relaxation of agonist-shortened individual smooth muscle cells, is apparently concealed by the tension-related relaxation in the preparation of tension-loaded whole tissues.
In conclusion, we demonstrated a novel mechanism of smooth muscle relaxation. It is suggested that PKC-dependent reorganization of actin cytoskeleton during agonist-induced contraction promotes spontaneous relaxation. Less
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Report
(3 results)
Research Products
(20 results)
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[Publications] Mita, M., Oishi, K., Hashimoto, T. and Uchida, M. K.: "Receptor desensitization and Ca-signaling" Uchida, M. K., Japan Scientific press, Tokyo, 213(p.21〜46) (1996)
