モルモット心室筋膜電流成分に対するデノパミンの選択的効果
モルモット単一心室筋細胞の膜電流をパッチクランプ法によって記録し, 選択的なβ1アゴニストとして知られているデノパミンの作用を調べた.デノパミン1μMは従来のβアゴニストと同様にLタイプのCaチャネル電流を約2倍に増大し, また遅延整流K電流を増大したが, 内向き整流K電流に対する効果はほとんどみられなかった.一方, イソプロテレノールによって誘発されるCl電流は, デノパミン1μMでは活1生化されず, 10μMでわずかに活性化を認めた.イソプロテレノールなどによるβ1刺激は, このCl電流活性化によって膜を脱分極し, 心室筋自発放電を誘発することが知られているが, デノパミンは上に述べたチャ...
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| Published in | 心電図 Vol. 10; no. 3; pp. 336 - 343 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本不整脈心電学会
1990
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0285-1660 1884-2437 |
| DOI | 10.5105/jse.10.336 |
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| Abstract | モルモット単一心室筋細胞の膜電流をパッチクランプ法によって記録し, 選択的なβ1アゴニストとして知られているデノパミンの作用を調べた.デノパミン1μMは従来のβアゴニストと同様にLタイプのCaチャネル電流を約2倍に増大し, また遅延整流K電流を増大したが, 内向き整流K電流に対する効果はほとんどみられなかった.一方, イソプロテレノールによって誘発されるCl電流は, デノパミン1μMでは活1生化されず, 10μMでわずかに活性化を認めた.イソプロテレノールなどによるβ1刺激は, このCl電流活性化によって膜を脱分極し, 心室筋自発放電を誘発することが知られているが, デノパミンは上に述べたチャネル選択性によって, このような作用が比較的弱いと考えられる. |
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| AbstractList | モルモット単一心室筋細胞の膜電流をパッチクランプ法によって記録し, 選択的なβ1アゴニストとして知られているデノパミンの作用を調べた.デノパミン1μMは従来のβアゴニストと同様にLタイプのCaチャネル電流を約2倍に増大し, また遅延整流K電流を増大したが, 内向き整流K電流に対する効果はほとんどみられなかった.一方, イソプロテレノールによって誘発されるCl電流は, デノパミン1μMでは活1生化されず, 10μMでわずかに活性化を認めた.イソプロテレノールなどによるβ1刺激は, このCl電流活性化によって膜を脱分極し, 心室筋自発放電を誘発することが知られているが, デノパミンは上に述べたチャネル選択性によって, このような作用が比較的弱いと考えられる. |
| Author | 石原, 圭子 野間, 昭典 松岡, 達 秦, 達意 |
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| References | 18) Reuter H: Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature 301: 569, 1983 19) Matsuura H, Ehara T, Imoto Y: An analysis of the delayed outward current in single ventricular cells of the guinea-pig. Pflügers Arch 410: 596, 1987 15) Powell T, Terrar DA, Twist VW: Electrical properties of individual cells isolated from adult rat ventricular myocardium. J Physiol 302: 131, 1980 9) Eagan TM, Noble D, Noble SJ, Powell T, Twist VW: An isoprenaline-activated sodium-dependent inward current in ventricular myocytes. Nature 328: 634, 1987 22) Sasaki Y, Yabana H, Nagao T, Takeyama S: Effect of denopamine on the phosphorylation of cardiac muscle proteins in the perfused guineapig heart: comparison with isoproterenol. Biochem Pharmacol 37: 679, 1988 7) 佐藤俊明, 今西愿, 有田眞: 新強心薬TA-064 (Denopamine) のモルモット心室筋に及ぼす陽性変力作用-Isoproterenol, Ouabainとの比較-. 薬理と治療13: 5727, 1985 5) Narita H, Yabana H, Kikkawa K, Miyazaki K, Ikeo T, Nagao T: Weak arrhythmogenic property of the new cardiotonic agent demopamine in dogs: Comparison with catecholamines. Japan J Pharmacol 41: 334, 1986 8) Irisawa H: Pacemaker mechanism of the mammalian heart. Jikeikai Med J 32: 157, 1985 14) Isenberg G, Klöckner U: Calcium tolerant ventricular myocytes prepared by preincubation in a “KB medium”. Pflügers Arch 395: 6, 1982 16) Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ: Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391: 85, 1981 6) 星山正夫, 池尾富弘, 宮崎聖, 長尾拓: ネコ摘出心筋におけるdenopamineの心収縮力, 拍動数に対する作用並びに自動能誘発作用. 薬理と治療13: 6323, 1985 11) Harvey RD, Hume JR: Autonomic regulation of a chloride current in heart. Science 244: 983, 1989 4) Ikeo T, Nagao T, Murata S, Yabana H, Sato M, Nakajima H: Cardiovascular effects of the new positive inotropic agent denopamine with special reference to species difference and the effect on failing heart. Arzneim-Forsh Drug Res 36: 1063, 1986 21) 長尾拓: 慢性心不全治療の実際新しい経口強心薬-デノパミン-その薬理作用-. Progress in Medicine 8: 467, 1988 23) Hedberg A, Carlsson E, Fellenius E, Lundgren B: Naunyn-Schmiedeberg's Cardiostimulatory effects of prenalterol, a Beta-1 adrenoceptor partial agonist, in vivo and in vitro. Archs Pharmac 318: 185, 1982 12) Bahinski A, Nairn AC, Greengard P, Gadsby DC: Chloride conductance regulated by cyclic AMP-dependent protein kinase in cardiac myocytes. Nature 340: 718, 1989 1) Inamasu M, Totsuka T, Ikeo T, Nagao T, Takeyama S: Beta1-adrenergic selectivity of the new cariotonic agent denopamine in its stimulating effects on adenylate cyclase. Biochem Pharmacol 36: 1947, 1987 3) Naito K, Nagao T, Ono Y, Otsuka M, Harigaya S, Nakajima H: Effect of GTP on the affinity of denopamine, a new cardiotonic agent, for β-adrenergic receptors of turkey erythrocytes and rat reticulocytemembranes. Japan J Pharmacol 39: 541, 1985 17) Soejima M, Noma A: Mode of regulation of the Ach-sensitive K-channel by the muscarinic receptor in rabbit atrial cells. Pflügers Arch 400: 424, 1984 20) Kameyama M, Hofmann F, Trautwein W: On the mechanism of β-adrenergic regulation of the Ca channel in the guinea-pig heart. Pflügers Arch 405: 285, 1985 10) Eagan TM, Noble D, Noble SJ, Powell T, Twist VW, Yamaoka K: On the mechanism of isoprenaline-and forskolin-induced depolarization of single guinea-pig ventricular myocytes. J Physiol 400: 299, 1988 2) Naito K, Nagao T, Otsuka M, Harigaya S, Nakajima H: Studies on the affinity and selectivity of denopamine (TA-064) , a new cardiotonic agent, for β-adrenergic receptors. Japan J Pharmacol 38: 235, 1985 13) Ehara T, Matsuoka S, Noma A: Chloride-sensitive nature of the epinephrine-induced current in guinea-pig cardiac myocytes (accepted for publication |
| References_xml | – reference: 6) 星山正夫, 池尾富弘, 宮崎聖, 長尾拓: ネコ摘出心筋におけるdenopamineの心収縮力, 拍動数に対する作用並びに自動能誘発作用. 薬理と治療13: 6323, 1985 – reference: 10) Eagan TM, Noble D, Noble SJ, Powell T, Twist VW, Yamaoka K: On the mechanism of isoprenaline-and forskolin-induced depolarization of single guinea-pig ventricular myocytes. J Physiol 400: 299, 1988 – reference: 23) Hedberg A, Carlsson E, Fellenius E, Lundgren B: Naunyn-Schmiedeberg's Cardiostimulatory effects of prenalterol, a Beta-1 adrenoceptor partial agonist, in vivo and in vitro. Archs Pharmac 318: 185, 1982 – reference: 4) Ikeo T, Nagao T, Murata S, Yabana H, Sato M, Nakajima H: Cardiovascular effects of the new positive inotropic agent denopamine with special reference to species difference and the effect on failing heart. Arzneim-Forsh Drug Res 36: 1063, 1986 – reference: 15) Powell T, Terrar DA, Twist VW: Electrical properties of individual cells isolated from adult rat ventricular myocardium. J Physiol 302: 131, 1980 – reference: 14) Isenberg G, Klöckner U: Calcium tolerant ventricular myocytes prepared by preincubation in a “KB medium”. Pflügers Arch 395: 6, 1982 – reference: 19) Matsuura H, Ehara T, Imoto Y: An analysis of the delayed outward current in single ventricular cells of the guinea-pig. Pflügers Arch 410: 596, 1987 – reference: 7) 佐藤俊明, 今西愿, 有田眞: 新強心薬TA-064 (Denopamine) のモルモット心室筋に及ぼす陽性変力作用-Isoproterenol, Ouabainとの比較-. 薬理と治療13: 5727, 1985 – reference: 18) Reuter H: Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature 301: 569, 1983 – reference: 2) Naito K, Nagao T, Otsuka M, Harigaya S, Nakajima H: Studies on the affinity and selectivity of denopamine (TA-064) , a new cardiotonic agent, for β-adrenergic receptors. Japan J Pharmacol 38: 235, 1985 – reference: 20) Kameyama M, Hofmann F, Trautwein W: On the mechanism of β-adrenergic regulation of the Ca channel in the guinea-pig heart. Pflügers Arch 405: 285, 1985 – reference: 21) 長尾拓: 慢性心不全治療の実際新しい経口強心薬-デノパミン-その薬理作用-. Progress in Medicine 8: 467, 1988 – reference: 16) Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ: Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391: 85, 1981 – reference: 3) Naito K, Nagao T, Ono Y, Otsuka M, Harigaya S, Nakajima H: Effect of GTP on the affinity of denopamine, a new cardiotonic agent, for β-adrenergic receptors of turkey erythrocytes and rat reticulocytemembranes. Japan J Pharmacol 39: 541, 1985 – reference: 13) Ehara T, Matsuoka S, Noma A: Chloride-sensitive nature of the epinephrine-induced current in guinea-pig cardiac myocytes (accepted for publication) – reference: 11) Harvey RD, Hume JR: Autonomic regulation of a chloride current in heart. Science 244: 983, 1989 – reference: 12) Bahinski A, Nairn AC, Greengard P, Gadsby DC: Chloride conductance regulated by cyclic AMP-dependent protein kinase in cardiac myocytes. Nature 340: 718, 1989 – reference: 22) Sasaki Y, Yabana H, Nagao T, Takeyama S: Effect of denopamine on the phosphorylation of cardiac muscle proteins in the perfused guineapig heart: comparison with isoproterenol. Biochem Pharmacol 37: 679, 1988 – reference: 17) Soejima M, Noma A: Mode of regulation of the Ach-sensitive K-channel by the muscarinic receptor in rabbit atrial cells. Pflügers Arch 400: 424, 1984 – reference: 5) Narita H, Yabana H, Kikkawa K, Miyazaki K, Ikeo T, Nagao T: Weak arrhythmogenic property of the new cardiotonic agent demopamine in dogs: Comparison with catecholamines. Japan J Pharmacol 41: 334, 1986 – reference: 8) Irisawa H: Pacemaker mechanism of the mammalian heart. Jikeikai Med J 32: 157, 1985 – reference: 9) Eagan TM, Noble D, Noble SJ, Powell T, Twist VW: An isoprenaline-activated sodium-dependent inward current in ventricular myocytes. Nature 328: 634, 1987 – reference: 1) Inamasu M, Totsuka T, Ikeo T, Nagao T, Takeyama S: Beta1-adrenergic selectivity of the new cariotonic agent denopamine in its stimulating effects on adenylate cyclase. Biochem Pharmacol 36: 1947, 1987 |
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| Snippet | モルモット単一心室筋細胞の膜電流をパッチクランプ法によって記録し, 選択的なβ1アゴニストとして知られているデノパミンの作用を調べた.デノパミン1μMは従... |
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| SubjectTerms | Ca電流 Cl電流 デノパミン 単一心室筋 膜電位固定実験 |
| Title | モルモット心室筋膜電流成分に対するデノパミンの選択的効果 |
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