Increased Inhibitory Effect of Phorbol Ester on Cytosolic Ca<SUP>2+</SUP> Level and Contraction in Rat Myometrium after Gestation
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概要
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Activation of voltage-dependent Ca<SUP>2+</SUP> channels by high K<SUP>+</SUP> (40 mM) increased the cyiosolic Ca<SUP>2+</SUP> level ([Ca<SUP>2+</SUP>]i) (estimated by fura-PE3 fluorescence ratio) and force in myometrium isolated from pregnant (21 days after gestation) and non-pregnant (estrus) rats. 12-Deoxyphorbol 13-isobutyrate (DPB, 1 mM) decreased the high K+_stimulated [Ca<SUP>2+</SUP>]i and force in a concentration-dependent manner. The inhibitory effect was stronger in the pregnant myometrium than in the non-pregnant myometrium. In the pregnant myometrium, the increase in Ca<SUP>2+</SUP> permeability by ionomycin (1 μM) greatly increased [Ca<SUP>2+</SUP>]i and force, which were only partially inhibited by verapamil (10 μM). DPB (1 μM) inhibited the verapamil-insensitive component of the increases in [Ca<SUP>2+</SUP>]i and muscle tension. Oxyiocin (100 nM) and thapsigargin (1 μM) also induced a verapamil-insensitive increase in [Ca<SUP>2+</SUP>]i and force, and DPB (1 μM) inhibited these increments. Ca<SUP>2+</SUP> sensitivity of contractile elements, estimated from the relationships between Ca<SUP>2+</SUP> and muscle force in intact and α-toxin permeabilized muscle, was not significantly changed by DPB (1 μM). In summary, DPB inhibits the increase in [Ca<SUP>2+</SUP>]i more strongly in myometrium isolated from pregnant rats than that from non-pregnant rats without any change in the [Ca<SUP>2+</SUP>]i/tension relationship. Since DPB decreased [Ca<SUP>2+]i-rise induced by three different mechanisms, DPB may activate Ca<SUP>2+</SUP> extrusion, rather than to inhibit a specific influx pathway, to decrease [Ca<SUP>2+</SUP>]i.
- 社団法人 日本薬理学会の論文
著者
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Hori M
Leaf Tobacco Research Center Japan Tobacco Inc.:(present Address)laboratory Of Insect Science And Bi
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Ozaki H
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences University Of
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Kim Bo-Kyung
Department of Veterinary Pharmacology. Graduate School of Agriculture and Llfe Sciences, The Univ
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Ozaki Hiroshi
Department of Veterinary Pharmacology. Graduate School of Agriculture and Llfe Sciences, The Univ
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Hori Masatoshi
Department of Veterinary Pharmacology. Graduate School of Agriculture and Llfe Sciences, The Univ
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Karaki Hideaki
Department of Veterinary Pharmacology. Graduate School of Agriculture and Llfe Sciences, The Univ
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Ozaki Hiroshi
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Ozaki Hiroshi
<I>Department of Veterinary Pharmacology. Graduate School of Agriculture and Llfe Sciences, The University of Tokyo</I>
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Karaki Hideaki
<I>Department of Veterinary Pharmacology. Graduate School of Agriculture and Llfe Sciences, The University of Tokyo</I>
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Kim Bo-Kyung
<I>Department of Veterinary Pharmacology. Graduate School of Agriculture and Llfe Sciences, The University of Tokyo</I>
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