Distinct Roles of Protein Kinase C Isoforms in Myogenic Constriction of Rat Posterior Cerebral Arteries
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概要
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The involvement of protein kinase C (PKC) in myogenic constriction at physiological intraluminal pressure was investigated in rat posterior cerebral arteries. Changes in constriction and intracellular Ca2+ concentration ([Ca2+]i) were measured in fura 2-loaded arterial segments by pressurized arteriography. When intraluminal pressure was raised from 5 to 60 mmHg and maintained for 60 min, sustained constriction and [Ca2+]i elevation were elicited. The constriction and [Ca2+]i at 60 mmHg gradually declined in the presence of RO31-8220, a general PKC inhibitor, and rottlerin, a PKCδ inhibitor. In contrast, Gö6976, a conventional PKC inhibitor, significantly diminished the constriction with no inhibition on the [Ca2+]i. In the presence of nicardipine, the pressure stimulation to 60 mmHg still produced a small sustained [Ca2+]i elevation. The nicardipine-insensitive [Ca2+]i elevation gradually declined in the presence of rottlerin, and it was nearly abolished by ruthenium red. Immunohistochemical analysis showed positive staining for PKCα, γ, δ, and ε, but not PKCβ, in smooth muscle cells of rat posterior cerebral arteries. These results suggest distinct roles of PKC isoforms in myogenic constriction: conventional PKC mediates Ca2+ sensitization, whereas PKCδ mediates sustained [Ca2+]i elevation via the activation of cation channels, resulting in sustained constriction.
- 社団法人 日本薬理学会の論文
- 2008-12-20
著者
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ISHIKAWA Tomohisa
Department of Neuropsychiatry, Ehime University Medical School
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KASHIHARA Toshihide
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka
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NAKAYAMA Koichi
Department of Molecular and Cellular Pharmacology, Faculty of Pharmaceutical Sciences, Iwate Medical
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Nakayama Koichi
Department Of Molecular And Cellular Pharmacology Faculty Of Pharmaceutical Sciences Iwate Medical U
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Nakayama Koichi
Department Of Cellular And Molecular Pharmacology Graduate School Of Pharmaceutical Sciences Univers
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Ishikawa Tomohisa
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences University Of Shizuoka
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Ishikawa Tomohisa
Department Of Cellular And Molecular Pharmacology Graduate School Of Pharmaceutical Sciences Univers
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Kashihara Toshihide
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences University Of Shizuoka
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Kashihara Toshihide
Department Of Cardiology Pulmonology And Nephrology Yamagata University School Of Medicine
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