α-Adrenoceptor Agonists Produce Ca^<2+> Oscillations in Isolated Rat Aorta : Role of Protein Kinase C
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概要
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We investigated the relationship between tension development and the cytosolic free Ca^<2+> level ([Ca^<2+>]_i) in responses to norepinephrine (NE) and selective α_2-adrenoceptor agonist, UK14,304 of the endothelium-denuded rat aorta loaded with fura PE-3. NE (3×10^<-8>M) evoked a rapid increase in [Ca^<2+>]_i followed by slight decreasing to a steady state level and produced a contraction. After the NE-induced increase in [Ca^<2+>]_i had reached a maximum, the [Ca^<2+>]_i showed persistent oscillations. The Ca^<2+> oscillations were superimposed on the sustained increase in [Ca^<2+>]_i. UK14,304 (3×10^<-6>M) also evoked an increase in [Ca^<2+>]_i and produced a contraction. However, the UK14,304-induced effect on [Ca^<2+>]_i was characterized by pronounced oscillations, and the amplitude of the sustained increase in [Ca^<2+>]_i was less than that seen with NE. Protein kinase C inhibitor, Ro31-8220 (3×10^<-6>M) and verapamil (10^<-5>M) abolished both NE- and UK14,304-evoked Ca^<2+> oscillations. UK14,304-induced contractions were also strongly inhibited by Ro31-8220 and verapamil. However, NE-induced contractions were partly inhibited by these inhibitors. The sustained increases in [Ca^<2+>]_i evoked NE and UK14,304 were not significantly inhibited by Ro31-8220 and verapamil. These results suggest that NE and UK14,304 produce Ca^<2+> oscillations during sustained contractions in rat aorta. The α_2-adrenoceptor agonist, UK14,304-induced sustained contraction and Ca^<2+> oscillations may be due to PKC activation and opening of voltage-dependent L-type Ca^<2+> channels.
- 日本平滑筋学会の論文
著者
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KAMATA Katsuo
Department of Pharmacology, School of Pharmacy, Hoshi University
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Kamata Katsuo
Department Of Pharmacology School Of Pharmacy Hoshi University:department Of Chemical Pharmacology F
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SUENAGA Hiroshi
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University
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Suenaga H
Hoshi Univ. Tokyo Jpn
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Suenaga Hiroshi
Department Of Physiology And Morphology Institute Of Medicinal Chemistry Hoshi University
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KAMATA Katsuo
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University
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