2種の硝酸薬のアフリカツメガエル発現L型Ca2+チャネルに対する薬物特異的作用
心筋L型Ca2+チャネルに対する作用を指標として, 2種の一酸化窒素 (NO) 供与体と2種の硝酸薬の作用を比較検討した.アフリカツメガエル卵母細胞に心筋L型Ca2+チャネルを発現させ, 発現したチャネルを通過するBa2+電流に対する各薬剤の作用を観察した.NO供与体である, S-nitroso-N-acetyl penicillamineとsodium nitroprussideはいずれも濃度依存性にBa2+電流を抑制し, その作用はcGMP依存性蛋白キナーゼ (PKG) 依存性であった.また, ニトログリセリン (NTG) も濃度依存性にBa2+電流を抑制し, 約100nMで最大抑制を示し...
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| Published in | 心電図 Vol. 23; no. 3; pp. 271 - 280 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English Japanese |
| Published |
一般社団法人 日本不整脈心電学会
25.05.2003
日本心電学会 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0285-1660 1884-2437 |
| DOI | 10.5105/jse.23.271 |
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| Abstract | 心筋L型Ca2+チャネルに対する作用を指標として, 2種の一酸化窒素 (NO) 供与体と2種の硝酸薬の作用を比較検討した.アフリカツメガエル卵母細胞に心筋L型Ca2+チャネルを発現させ, 発現したチャネルを通過するBa2+電流に対する各薬剤の作用を観察した.NO供与体である, S-nitroso-N-acetyl penicillamineとsodium nitroprussideはいずれも濃度依存性にBa2+電流を抑制し, その作用はcGMP依存性蛋白キナーゼ (PKG) 依存性であった.また, ニトログリセリン (NTG) も濃度依存性にBa2+電流を抑制し, 約100nMで最大抑制を示した (21±5%, n=11) .また同抑制はNO消去薬であるcarboxy-PITOにより消失した.一方, 二硝酸イソソルビド (ISDN) は単純な濃度依存性抑制作用を示さず, 電流は減少または増加した (n=16) , しかし, carboxy-PITO存在下にISDNを作用させると同電流は常に増加し, その増加率は10μMで19.4%であった (n=6) .NTGならびにISDNはNO供与体として発現心筋L型Ca2+チャネルを抑制する作用を有すると考えられた.また, ISDNはこの作用に加えてNOに依存しないCa2+チヤネル刺激作用を有すると考えられ, NTGと比較して陰性変力作用が弱いことの一因となっていることが示唆された. |
|---|---|
| AbstractList | 心筋L型Ca2+チャネルに対する作用を指標として, 2種の一酸化窒素 (NO) 供与体と2種の硝酸薬の作用を比較検討した.アフリカツメガエル卵母細胞に心筋L型Ca2+チャネルを発現させ, 発現したチャネルを通過するBa2+電流に対する各薬剤の作用を観察した.NO供与体である, S-nitroso-N-acetyl penicillamineとsodium nitroprussideはいずれも濃度依存性にBa2+電流を抑制し, その作用はcGMP依存性蛋白キナーゼ (PKG) 依存性であった.また, ニトログリセリン (NTG) も濃度依存性にBa2+電流を抑制し, 約100nMで最大抑制を示した (21±5%, n=11) .また同抑制はNO消去薬であるcarboxy-PITOにより消失した.一方, 二硝酸イソソルビド (ISDN) は単純な濃度依存性抑制作用を示さず, 電流は減少または増加した (n=16) , しかし, carboxy-PITO存在下にISDNを作用させると同電流は常に増加し, その増加率は10μMで19.4%であった (n=6) .NTGならびにISDNはNO供与体として発現心筋L型Ca2+チャネルを抑制する作用を有すると考えられた.また, ISDNはこの作用に加えてNOに依存しないCa2+チヤネル刺激作用を有すると考えられ, NTGと比較して陰性変力作用が弱いことの一因となっていることが示唆された. 心筋L型Ca2+チャネルに対する作用を指標として, 2種の一酸化窒素(NO)供与体と2種の硝酸薬の作用を比較検討した. アフリカツメガエル卵母細胞に心筋L型Ca2+チャネルを発現させ, 発現したチャネルを通過するBa2+電流に対する各薬剤の作用を観察した. NO供与体である, S-nitroso-N-acetyl penicillamineとsodium nitroprussideはいずれも濃度依存性にBa2+電流を抑制し, その作用はcGMP依存性蛋白キナーゼ(PKG)依存性であった. また, ニ卜ログリセリン(NTG)も濃度依存性にBa2+電流を抑制し, 約100nMで最大抑制を示した(21±5%, n=11). また同抑制はNO消去薬であるcarboxy-PIT0により消失した. 一方, 二硝酸イソソルビド(ISDN)は単純な濃度依存性抑制作用を示さず, 電流は減少または増加した(n=16). しかし, carboxy-PITO存在下にISDNを作用させると同電流は常に増加し, その増加率は10μMで19.4%であった(n=6). NTGならびにISDNはNO供与体として発現心筋L型Ca2+チャネルを抑制する作用を有すると考えられた. また, ISDNはこの作用に加えてNOに依存しないCa2+チャネル刺激作用を有すると考えられ, NTGと比較して陰性変力作用が弱いことの一因となっていることが示唆された. (心電図, 2003;23:271～280) |
| Author | 渡邉, 英憲 神谷, 奈津子 一色, 高明 古川, 泰司 斉藤, 雅彦 竹下, 聡 中臺, 司 |
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| References | 2) Kawamoto JH, McLaughlin BE, Brien JF, Marks GS, Nakatsu K: Biotransformation of glyceryl trinitrate and elevation of cyclic GMP precede glyceryl trinitrateinduced vasodilation. J Cardiovasc Pharmacol, 1990; 15: 714-719 16) Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca (2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Then, 1999; 291: 464-473 10) Gunnar RM, Bourdillon PD, Dixon DW, Foster V, Karp RB, Kennedy JW, Klocke FJ, Passamani ER, Pitt B, Rapaport E, et al.: ACC/AHA guidelines for the early management of patients with acute myocardial infarction. A report of the American College of Cardiology American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (subcommittee to develop guidelines for the early management of patients with acute myocardial infarction) . Circulation, 1990; 82: 664-707 26) Blumenstein Y, Ivanina T, Shistik E, Bossi E, Peres A, Dascal N: Regulation of cardiac L-type Ca2+ channel by coexpression of G (alpha s) in Xenopus oocytes. FEBS Lett, 1999; 444: 78-84 13) Mery P-F, Pavoine C, Belhassen L, Pecker F, Fischmeister R: Nitric oxide regulated cardiac Ca2+ current. J Biological Chemistry, 1993; 268: 26286-26295 7) Toyoda J, Hisayama T, Takayanagi I: Effects of nitro compounds, isosorbide dinitrate, 5-isosorbide mononitrate and glyceryl trinitrate on Ca-uptake into Ca-stores and Ca-release from Ca-stores in rabbit isolated femoral veins and femoral arteries. Gen Pharmacol, 1987; 18: 95-97 21) Hamaguchi M, Ishibashi T, Imai S: Involvement of charybdotoxin-sensitive K+ channel in the relaxation of bovine tracheal smooth muscle by glyceryl trinitrateand sodium nitroprusside. J Pharmacol Exp Then, 1992; 262: 263-270 27) Tsien RW, Bean BP, Hess P, Lansman JB, Nilius B, Nowycky MC: Mechanisms of calcium channel modulation by beta-adrenergic agents and dihydropyridine calcium agonists. J Mol Cell Cardiol, 1986; 18: 691-710 4) Stiefel A, Kreye VA: On the haemodynamic differences between sodium nitroprusside, nitroglycerin, and isosorbide nitrates. Comparison of their vasorelaxant effects in vitro and of their inactivation in vivo. Naunyn Schmiedebergs Arch Pharmacol, 1984; 325: 270-274 17) Jiang LH, Gawler DJ, Hodson N, Milligan CJ, Pearson HA, Porter V, Wray D: Regulation of cloned cardiac L-type calcium channels by cGMP-dependent protein kinase. J Biol Chem, 2000: 275: 6135-6143 19) Perets T, Blumenstein Y, Shistik E, Lotan I, Dascal N: A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel alpha 1C subunit. FEBS Lett, 1996 384: 189-192 23) Mery P-F, Lohmann SM, Walter U, Fischmeister R Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes. Proc Natl Acad Sci USA, 1991; 88: 1197-1201 11) Cohn JN, Archibald DG, Ziesche S, Franciosa JA, Harston WE, Tristani FE, Dunkman WB, Jacobs W, Francis GS, Flohr KH, et al.: Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1986: 314: 154-1552 6 ) Muikku O, Hynynen M, Salmenpera M, Heinonen J: Vasodilator properties of nitroglycerin and isosorbide dinitrate during cardiopulmonary bypass. Br J Anaesth, 1992; 68: 376-380 12) Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F, Smith R, Dunkman WB, Loeb H, Wong M, et al.: A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure [see comments] . N Engl J Med, 1991; 325: 303-310 14) Mikami A, Imoto K, Tanabe T, Niidome T, Mori Y, Takeshima H, Narumiya S, Numa S: Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel. Nature, 1989: 340: 230-233 15) Mori Y, Friedrich T, Kim M-S, Mikami A, Nakai J, Ruth P, Bosse E, Hofmann F, Flockerzi V, Furuichi T, Mikoshiba K, Imoto K, Tanabe T, Numa S: Primary structure and functional expression from complementary DNA of a brain calcium channel. Nature, 1991; 350: 398-402 1) Ignarro LJ: Biological actions and properties of endothelium-derived nitric oxide formed and released from artery and vein. Circ Res, 1989: 65: 1-21 18) Singer-Lahat D, Lotan I, Biel M, Flockerzi V, Hofmann F, Dascal N: Cardiac calcium channels expressed in Xenopus oocytes are modulated by dephosphorylation but not by cAMP-dependent phosphorylation. Receptors Channels, 1994; 2: 215-226 24) Morrison RA, Wiegand UW, Jahnchen E, Hohmann D, Bechtold H, Meinertz T, Fung HL: Isosorbide dinitrate kinetics and dynamics after intravenous, sublingual, and percutaneous dosing in angina. Clin Pharmacol Then, 1983; 33: 747-756 3) Kreye VA, Stiefel A: In vivo and in vitro studies to elucidate the hemodynamic differences of sodium nitroprusside, nitroglycerin, and two isosorbide nitrates. Z Kardiol, 1983; 72: 52-55 20) Chen XL, Rembold CM: Cyclic nucleotide-dependent regulation of Mn2+ influx, [Ca2+] i, and arterial smooth muscle relaxation. Am J Physiol, 1992; 263: C468-C473 5) Muikku O, Hynynen M, Salmenpera M, Harjula A, Heinonen J: Pulmonary vascular effects of trinitroglycerin and isosorbide dinitrate after cardiopulmonary bypass. Br J Anaesth, 1993; 71: 720-724 25) Santoni Y, Iliadis A, Cano JP, Luccioni R, Frances Y: Pharmacokinetics of isosorbide dinitrate and its mononitrate metabolites after intravenous infusion. J Pharmacokinet Biopharm, 1986; 14: 1-17 9) Durrer JD, Lie KI, van Capelle FJ, Durrer D: Effect of sodium nitroprusside on mortality in acute myocardial infarction. N Engl J Med. 1982; 306: 1121-1128 22) Perez-Vizcaino F, Villamor E, Duante J, Tamargo J: Involvement of protein kinase C in reduced relaxant responses to the NO/cyclic GMP pathway in piglet pulmonary arteries contracted by the thromboxane A2-mimetic U46619. Br J Pharmacol, 1997; 121: 1323-1333 8) Jugdutt BI, Warnica JW: Intravenous nitroglycerin therapy to limit myocardial infarct size, expansion, and complications. Effect of timing, dosage, and infarct location [published erratum appears in Circulation 1989 May: 79 (5) : 1151] . Circulation, 1988: 78: 906-919 |
| References_xml | – reference: 11) Cohn JN, Archibald DG, Ziesche S, Franciosa JA, Harston WE, Tristani FE, Dunkman WB, Jacobs W, Francis GS, Flohr KH, et al.: Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1986: 314: 154-1552 – reference: 1) Ignarro LJ: Biological actions and properties of endothelium-derived nitric oxide formed and released from artery and vein. Circ Res, 1989: 65: 1-21 – reference: 13) Mery P-F, Pavoine C, Belhassen L, Pecker F, Fischmeister R: Nitric oxide regulated cardiac Ca2+ current. J Biological Chemistry, 1993; 268: 26286-26295 – reference: 18) Singer-Lahat D, Lotan I, Biel M, Flockerzi V, Hofmann F, Dascal N: Cardiac calcium channels expressed in Xenopus oocytes are modulated by dephosphorylation but not by cAMP-dependent phosphorylation. Receptors Channels, 1994; 2: 215-226 – reference: 7) Toyoda J, Hisayama T, Takayanagi I: Effects of nitro compounds, isosorbide dinitrate, 5-isosorbide mononitrate and glyceryl trinitrate on Ca-uptake into Ca-stores and Ca-release from Ca-stores in rabbit isolated femoral veins and femoral arteries. Gen Pharmacol, 1987; 18: 95-97 – reference: 4) Stiefel A, Kreye VA: On the haemodynamic differences between sodium nitroprusside, nitroglycerin, and isosorbide nitrates. Comparison of their vasorelaxant effects in vitro and of their inactivation in vivo. Naunyn Schmiedebergs Arch Pharmacol, 1984; 325: 270-274 – reference: 8) Jugdutt BI, Warnica JW: Intravenous nitroglycerin therapy to limit myocardial infarct size, expansion, and complications. Effect of timing, dosage, and infarct location [published erratum appears in Circulation 1989 May: 79 (5) : 1151] . Circulation, 1988: 78: 906-919 – reference: 5) Muikku O, Hynynen M, Salmenpera M, Harjula A, Heinonen J: Pulmonary vascular effects of trinitroglycerin and isosorbide dinitrate after cardiopulmonary bypass. Br J Anaesth, 1993; 71: 720-724 – reference: 16) Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca (2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Then, 1999; 291: 464-473 – reference: 26) Blumenstein Y, Ivanina T, Shistik E, Bossi E, Peres A, Dascal N: Regulation of cardiac L-type Ca2+ channel by coexpression of G (alpha s) in Xenopus oocytes. FEBS Lett, 1999; 444: 78-84 – reference: 20) Chen XL, Rembold CM: Cyclic nucleotide-dependent regulation of Mn2+ influx, [Ca2+] i, and arterial smooth muscle relaxation. Am J Physiol, 1992; 263: C468-C473 – reference: 24) Morrison RA, Wiegand UW, Jahnchen E, Hohmann D, Bechtold H, Meinertz T, Fung HL: Isosorbide dinitrate kinetics and dynamics after intravenous, sublingual, and percutaneous dosing in angina. Clin Pharmacol Then, 1983; 33: 747-756 – reference: 6 ) Muikku O, Hynynen M, Salmenpera M, Heinonen J: Vasodilator properties of nitroglycerin and isosorbide dinitrate during cardiopulmonary bypass. Br J Anaesth, 1992; 68: 376-380 – reference: 23) Mery P-F, Lohmann SM, Walter U, Fischmeister R Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes. Proc Natl Acad Sci USA, 1991; 88: 1197-1201 – reference: 12) Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F, Smith R, Dunkman WB, Loeb H, Wong M, et al.: A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure [see comments] . N Engl J Med, 1991; 325: 303-310 – reference: 27) Tsien RW, Bean BP, Hess P, Lansman JB, Nilius B, Nowycky MC: Mechanisms of calcium channel modulation by beta-adrenergic agents and dihydropyridine calcium agonists. J Mol Cell Cardiol, 1986; 18: 691-710 – reference: 21) Hamaguchi M, Ishibashi T, Imai S: Involvement of charybdotoxin-sensitive K+ channel in the relaxation of bovine tracheal smooth muscle by glyceryl trinitrateand sodium nitroprusside. J Pharmacol Exp Then, 1992; 262: 263-270 – reference: 14) Mikami A, Imoto K, Tanabe T, Niidome T, Mori Y, Takeshima H, Narumiya S, Numa S: Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel. Nature, 1989: 340: 230-233 – reference: 17) Jiang LH, Gawler DJ, Hodson N, Milligan CJ, Pearson HA, Porter V, Wray D: Regulation of cloned cardiac L-type calcium channels by cGMP-dependent protein kinase. J Biol Chem, 2000: 275: 6135-6143 – reference: 10) Gunnar RM, Bourdillon PD, Dixon DW, Foster V, Karp RB, Kennedy JW, Klocke FJ, Passamani ER, Pitt B, Rapaport E, et al.: ACC/AHA guidelines for the early management of patients with acute myocardial infarction. A report of the American College of Cardiology American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (subcommittee to develop guidelines for the early management of patients with acute myocardial infarction) . Circulation, 1990; 82: 664-707 – reference: 22) Perez-Vizcaino F, Villamor E, Duante J, Tamargo J: Involvement of protein kinase C in reduced relaxant responses to the NO/cyclic GMP pathway in piglet pulmonary arteries contracted by the thromboxane A2-mimetic U46619. Br J Pharmacol, 1997; 121: 1323-1333 – reference: 3) Kreye VA, Stiefel A: In vivo and in vitro studies to elucidate the hemodynamic differences of sodium nitroprusside, nitroglycerin, and two isosorbide nitrates. Z Kardiol, 1983; 72: 52-55 – reference: 2) Kawamoto JH, McLaughlin BE, Brien JF, Marks GS, Nakatsu K: Biotransformation of glyceryl trinitrate and elevation of cyclic GMP precede glyceryl trinitrateinduced vasodilation. J Cardiovasc Pharmacol, 1990; 15: 714-719 – reference: 19) Perets T, Blumenstein Y, Shistik E, Lotan I, Dascal N: A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel alpha 1C subunit. FEBS Lett, 1996 384: 189-192 – reference: 25) Santoni Y, Iliadis A, Cano JP, Luccioni R, Frances Y: Pharmacokinetics of isosorbide dinitrate and its mononitrate metabolites after intravenous infusion. J Pharmacokinet Biopharm, 1986; 14: 1-17 – reference: 9) Durrer JD, Lie KI, van Capelle FJ, Durrer D: Effect of sodium nitroprusside on mortality in acute myocardial infarction. N Engl J Med. 1982; 306: 1121-1128 – reference: 15) Mori Y, Friedrich T, Kim M-S, Mikami A, Nakai J, Ruth P, Bosse E, Hofmann F, Flockerzi V, Furuichi T, Mikoshiba K, Imoto K, Tanabe T, Numa S: Primary structure and functional expression from complementary DNA of a brain calcium channel. Nature, 1991; 350: 398-402 |
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| Snippet | 心筋L型Ca2+チャネルに対する作用を指標として, 2種の一酸化窒素 (NO) 供与体と2種の硝酸薬の作用を比較検討した.アフリカツメガエル卵母細胞に心筋L型Ca2+チャネルを発現させ, 発現したチャネルを通過するBa2+電流に対する各薬剤の作用を観察した.NO供与体である, S-nitroso-N-acetyl... 心筋L型Ca2+チャネルに対する作用を指標として, 2種の一酸化窒素(NO)供与体と2種の硝酸薬の作用を比較検討した. アフリカツメガエル卵母細胞に心筋L型Ca2+チャネルを発現させ, 発現したチャネルを通過するBa2+電流に対する各薬剤の作用を観察した. NO供与体である, S-nitroso-N-acetyl... |
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| SubjectTerms | アフリカツメガエル卵母細胞 カルシウムチャネル 一酸化窒素 硝酸薬 |
| Title | 2種の硝酸薬のアフリカツメガエル発現L型Ca2+チャネルに対する薬物特異的作用 |
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| ispartofPNX | 心電図, 2003/05/25, Vol.23(3), pp.271-280 |
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