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2001 Fiscal Year Final Research Report Summary

Mechanisms responsible for MaxiK_<Ca> channel-mediated vascular relaxation

Research Project

Project/Area Number 12672226
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionToho University

Principal Investigator

TANAKA Yoshio  Toho University School of Pharmaceutical Science, Department of Pharmacology, Assistant Professor, 薬学部, 講師 (60188349)

Project Period (FY) 2000 – 2001
KeywordsMaxiK_<Ca> channel / IP receptor / Beraprost / cAMP / Gs protein / Cholera toxin / Iberiotoxin / Adenylyl cyclase
Research Abstract

The intracellular pathway(s) controlling vascular relaxation/induced by a prostaglandin I_2 (PGI_2b, IP) agonist beraprost was investigated. Beraprost-induced relaxation of guinea-pig aorta was almost abolished in high-KCl-contracted tissue, indicating a major role of K^+ conductances in the vascular reponse. Beraprost-induced relaxation was also practically abolished by a selective MaxiK_<Ca> channel blocker, Iberiotoxin (10^<-7> M). The relaxation induced by beraprost was not significantly affected by other K^+ channel blockers glibenclamide or Ba^<2+>, but was slightly attenuated by 4-aminopyridine. Beraprost increased intracellular cANP levels, suggesting a role for cAMP-dependent pathways. RO-20-1724, a selective inhibitor of cAMP-specific phosphodiesterase, significantly potentiated beraprost-induced vascular relaxation. Iberiotoxin completely counteracted this potentiation. Moreover, tension decrement due to forskolin or 8-bromo-cyclic AMP was thoroughly restored by the toxin, c … More onfirming a role for a cAMP-dependent mechanism. However, SQ 22,536, an adenylyl cyclase inhibitor, did not affect beraprost-induced vascular relaxation though it almost totally inhibited the elevation of cAMP contents induced by beraprost, which suggests the existence of cyclic AMP-independent mechanism. Moreover, cholera toxin, an activator of the stimulatory G protein of adenylyl cyclase (Gs), significantly inhibited PGF_<2α>-induced contraction both in the absence and presence of SQ 22,536. Iberiotoxin was also capable of restoring the relaxation induced by cholera toxin. These findings suggest that MaxiK_<Ca> channel plays a central role in mediating smooth muscle relaxation following stimulation of IP receptor with beraprost in guinea-pig aorta. Both cyclic AMP-dependent and -independent pathways contribute to the MaxiK_<Ca> channel-mediated relaxation following IP receptor stimulation in this vascular tissue. Direct regulation of MaxiK_<Ca> channels by Gs partly accounts for the cyclic AMP-independent relaxant mechanism. Less

  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Tanaka Y, Someya S, Tanaka H, Tsuru H, Shigenobu K: "Potentiation of stretch-induced tone in the rabbit facial vein by an isoquinoline derivative, LOE 908"Naunyn-Schmiedeberg's ArCh.Pharmacol.. 362(6). 577-580 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka Y, Igarashi T, Kaneko H, Yamaki F, Mochizuki Y, Aida M, Taniguchi H, Tanaka H, Shigenobu K: "NO-mediated MaxiK_<ca>, channel activation produces relaxation of guinea pig aorta independently of voltage-dependent L-type Ca^<2+> channels"Gen.Pharmacol.The Vascular System. 34(3). 159-165 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka Y, Hayakawa S, Imai T, Akutsu A, Hirano H, Tanaka H, Nakahara T, Ishii K, Shigenobu K: "Possible involvement of endothelium-derived hyperpolarizing factor (EPHF) in the depressor responses to platelet activating factor(PAF) in rats"Br.J.Pharmacol.. 131(6). 1113-1120 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka Y, Imai T, Igarashi T, Takayanagi K, Otsuka K, Yamaki F, Tanaka H, Shigenobu K: "Comparison of the Ca^<2+> entry channels responsible for mechanical responses of guinea-pig aorta to noradrenaline and thapsigargin using SK&F 96365 and LOE908"Naunyn-Schmiedeberg's Arch.Pharmacol.. 362(2). 160-168 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masumiya H, Tanaka Y, Tanaka H, Shigenobu K: "Inhibition of T-type and L-type Ca^<2+> currents by aranidipine, a novel hihydropyridine Ca^<2+> antagonist"Pharmacology. 61(2). 57-61 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakahara T, Moriuehi H, Yunoki M, Kubota Y, Tanaka Y, Sakamato K, Shigenobu K, Ishii K: "Involvement of K^+ channel in procainamide-induced relaxation of bovine tracheal smooth muscle"Eur.J.Pharmacol.. 402(1-2). 143-149 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishimaru K, Tanaka Y, Tanaka H, Shigenobu K: "Positive and negative inotropic effects of muscarinic receptor stimulation in mouse left atria"Life Sci.. 66(7). 607-615 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masumiya H, Matsuda T, Tanaka Y, Tanaka H, Shigenobu K: "Possible requirement of phosphonate moiety for efonidipine effects on the sino-atrial node action potential"Life Sci.. 66(16). PL239-PL244 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka Y, Kamibayashi M, Yamaki F, Saitoh M, Nakazawa T, Tanaka H, Noguchi K, Hashimoto K, Shigenobu K: "Relaxant action of azulene-1-carboxamidine derivative N^1 N^1-dimethyl-N^2-(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene-1-carboxamidine (HNS-32) in pig coronary artery"Phar.Pharmacol.Commun.. 6. 397-404 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamaki, F., Tanaka, H., Shigenobu, K., Tanaka, Y.: "Nitric Oxide accounts for endothelium-dependent relaxation of pig coronary artery in response to noradrenaline"Phar.Pharmacol.Commun.. 6. 195-199 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishimaru K, Kobayashi M, Matsuda T, Tanaka Y, Yamada H, Shigenobu K: "α-Adrenoceptor stimulation-mediated negative inotropism and enhanced Na^+/Ca^<2+> exchange in mouse ventricle"Am.J.Physiol.(Heart Circ.Physiol.). 280. H132-H141 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuda T, Masumiya H, Tanaka N, Yamashita T, Tsuruzoe N, Tanaka Y, Tanaka H, Shigenobu K: "Inhibition by a novel anti-arrhythmic agent, NIP-142, of cloned human cardiac K^+ channel Kv1.5 current"Life Sci.. 68(17). 2017-2024 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamaki F, Kaga M, Horinouchi T, Tanaka H, Koike K, Shigenobu K, Toro L, Tanaka Y: "MaxiK channel-mediated relaxation of guinea-pig aorta following stimulation of IP receptor with beraprost via cyclic AMP-dependent and -independent mechanisms"Naunyn-Schmiedeberg's Arch.Pharmacol.. 364(6). 538-550 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka Y, Shigenobu K, Nakayama K.: "Effects of endothelin-1 on the myogenic contraction of canine cerebral artery in response to quick stretch"Res.Commun.Mol.Pathol.Pharmacol.. 109(1-2). 95-101 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka Y, Mitani A, Igarashi T, Someya S, Otsuka K, Imai T Yamaki F, Tanaka H, Saitoh M, Nakazawa T, Noguchi K, Hashimoto K, Shigenobu K: "HNS-32, a novel azulene-1-carboxamidine derivative, inhibits nifedipine-sensitive and -insensitive contraction of the isolated rabbit aorta"Naunyn-Schmiedeberg's Arch.Pharmacol.. 363(3). 344-352 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imai T, Okamoto T, Yamamoto Y, Tanaka H, Koike K, Shigenobu K, Tanaka Y: "Effects of different types of K^+ channel modulators on the spontaneous myogenic contraction by guinea-pig urinary bladder smooth muscle"Acta Physiol.Scand.. 173(3). 323-334 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakahara T, Moriuchi H, Tanaka Y, Yunoki M, Kubota Y, Sakamoto K, Shigenobu K, Ishii K: "Role of K^+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal smooth muscle"Eur.J.Pharmacol.. 415(1). 73-78 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka Y, Kamibayashi M, Someya S, Yamaki F, Tanaka H, Shigenobu K: "Potentiation by melatonin of 5-hydroxytryptamine-induced contraction in pig coronary artery"Res.Commun.Pharmacol.Toxicol.. 6(1&2). 47-57 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka H, Nishimaru K, Kobayashi M, Matsuda T, Tanaka Y, Shigenobu K.: "Acetylcholine-induced positive inotropy mediated by prostaglandin released from endocardial endothelium in mouse left atrium"Naunyn-Schmiedeberg's Arch.Pharmacol.. 363(5). 577-582 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Noguchi K, Ito C, Isobe Y, Fukushima K, Tanaka Y, Tanaka H, Shigenobu K: "Effects of 5-HT_4 receptor agonist prokinetic agents on the action potential parameters of isolated rabbit myocardium"Pharmacology. 62(2). 73-79 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishimaru K, Makuta R, Tanaka Y, Tanaka H, Shigenobu K.: "Pharmacological properties of excitation-contraction mechanisms in isolated mouse left atria"Pharmacology. 62(2). 87-91 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka Y, Kamibayashi M, Imai T, Yamashita Y, Tanaka H, Nakahara T, Ishii K, Shigenobu K.: "Evidence for the possible involvement of Ca^<2+> entry blockade in the relaxation by class I antiarrhythmic drugs in the isolated pig coronary smooth muscle"Naunyn-Schmiedeberg's Arch.Pharmacol.. 365. 56-66 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka Y, Someya S, Tanaka H, Tsuru H & Shigenobu K: "Potentiation of stretch-induced tone in the rabbit facial vein by an isoquinoline derivative, LOE 908"Naunyn-Schmicdeberg's Arch. Pharmacol. 362(6). 577-580 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka Y, Igarashi T, Kaneko H, Yamaki F, Mochizuki Y, Aida M, Taniguchi H, Tanaka H & Shigenobu K: "NO-mediated MaxiK_<Ca>, channel activation produces relaxation of guinea pig aorta independently of voltage-dependent L-type Ca^<2+> channels"Gen. Pbarmacol. The Vascular System. 34(3). 159-165 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka Y, Hayakawa S, Imai T, Akutsu A, Hirano H, Tanaka H, Nakahara T,Ishii K & Shigenobu K: "Possible involvement of endothelium-derived hyperpolarizing factor (EDHF) in the depressor responses to platelet activating factor (PAF) in rats"Br. J. Pharmacol.. 131(6). 1113-1120 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka Y, Imai T, Igarashi T, Takayanagi K, Otsuka K, Yamaki F, Tanaka H & Shigenobu K: "Comparison of the Ca^<2+> entry channels responsible for mechanical responses of guinea-pig aorta to noradrenaline and thapsigargin using SK&F96365 and LOE908"Naunyn-Schmicdeberg's Arch. Pharmacol. 362(2). 160-168 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masumiya H,Tanaka Y,Tanaka H & Shigenobu K: "Inhibition of T-type and L-type Ca^<2+> currents by aranidipine, a novel hihydropyridine Ca^<2+> antagonist"Pharmacology. 61(2). 57-61 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakahara T, Moriuchi H, Yunoki M, Kubota Y, Tanaka Y, Sakamato K, Shigenobu K & Ishii K: "Involvement of K^+ channel in procainamide-induced relaxation of bovine tracheal smooth muscle"Eur. J. Pharmacol.. 402(1-2). 143-149 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimaru K, Tanaka Y, Tanaka H & Shigenobu K: "Positive and negative inotropic effects of muscarinic receptor stimulation in mouse left atria"Life Sci.. 66(7). 607-615 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masumiya H, Matsuda T. Tanaka Y. Tanaka H & Shigenobu K: "Possible requirement of phosphonate moiety for efonidipine effects on the sino-atrial node action potential"Life Sci.. 66(16). PL239-PL244 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka Y, Kamibayashi M, Yamaki F, Saitoh M, Nakazawa T, Tanaka , H, Noguchi K, Hashimoto K & Shigenobu K: "Relaxant action of azulene-I-carboxamidine derivative N^1,N^1-dimethyl-N^2-(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene-1-carboxamidine (HNS-32) in pig coronary artery"Phar. Pharmacol. Commun.. 6. 397-404 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamaki, R, Tanaka, H., Shigenobu, K., & Tanaka, Y.: "Nitric Oxide accounts for endothelium-dependent relaxation of pig coronary artery in response to noradrenaline"Phar. Pharmacol. Commun.. 6. 195-199 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimaru K, Kobayashi M, Matsuda T, Tanaka Y, Tanaka H & Shigenobu K: "α-Adrenoceptor stimulation-mediated negative inotropism and enhanced Na^+/Ca^<2+> exchange in mouse ventricle"Am. J. Physiol. (Heart Circ. Physiol). 280. H132-H141 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuda T, Masumiya H, Tanaka N, Yamashita T, Tsuruzoe N, Tanaka Y,Tanaka H & Shigenobu K: "Inhibition by a novel anti-arrhythmic agent, NIP-142, of cloned human cardiac K^+ channel Kv1.5 current"Life Sci.. 68(17). 2017-2024 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamaki F, Kaga M, Horinouchi T, Tanaka H, Koike K, Shigenobu K, Toro L & Tanaka Y: "MaxiK channel-mediated relaxation of guinea-pig aorta following stimulation of IP receptor with beraprost via cyclic AMP-dcpendent and -independent mechanisms"Naunyn-Schmicdeberg's Arch. Pharmacol. 364(6). 538-550 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka Y, Shigenobu K, Nakayama K.: "Effects of endothelin-1 on the myogenic contraction of canine cerebral artery in response to qnick stretch"Res. Commun. Mol. Pathol. Pharmacol.. 109(1-2). 95-101 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka Y, Mitani A, Igarashi T, Someya S, Otsuka K, Imai T, Yamaki F, Tanaka H, Saitoh M, Nakazawa T, Noguchi K, Hashimoto K & Shigeoobu K: "HNS-32, a novel azulene-1-carboxamidine derivative, inhibits nifedipinc-sensitive and -insensitive contraction of the isolated rabbit aorta"Naunyn-Schmiedeberg's Arch. Pharmacol.. 363(3). 344-352 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imai T, Okamoto T, Yamamoto Y, Tanaka H, Koike K, Shigenobu K & Tanaka Y: "Effects of different types of K^+ channel modulators on the spontaneous myogenic contraction of guinea-pig urinary bladder smooth muscle"Acta Physiol. Scand.. 173 (3). 323-334 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakahara T, Moriuchi H, Tanaka Y, Yunoki M, Kubota Y, Sakamato K, Shigenobu K & Ishii K: "Role of K^+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal smooth muscle"Eur. J. Pharmacol.. 415(1). 73-78 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka Y, Kamibayashi M, Someya S, Yamaki F, Tanaka H & Shigenobu K: "Potentiation by melatonin of 5-hydroxytryptamine-induced contraction in pig coronary artery"Res. Commun. Pharmacol. Toxicol.. 6(1&2). 47-57 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka H, Nishimaru K, Kobayashi M, Matsuda T, Tanaka Y, & Shigcnobu K: "Acetylcholine-induced positive inotropy mediated by prostaglandin released from endocardial endothelium in mouse left atrium"Naunyn-Schmiedeberg's Arch. Pharmacol.. 363(5). 577-582 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Noguchi K, Ito C, Isobe Y, Fukushima K, Tanaka Y, Tanaka H & Shigcnobu K: "Effects of 5-HT_4 receptor agonist prokinetic agents on the action potential parameters of isolated rabbit myocardium"Pharmacology. 62(2). 73-79 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimaru K, Makuta R, Tanaka Y, Tanaka H & Shigenobu K: "Pharmacological properties of excitation-contraction mechanisms in isolated mouse left atria"Pharmacology. 62(2). 87-91 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka Y, Kamibayashi M, Imai T, Yamashita Y, Tanaka H, Nakahara T, Ishii K & Shigenobu K.: "Evidence for the possible involvement of Ca^<2+> entry blockade in the relaxation by class I antiarrhythmic drugs in the isolated pig coronary smooth muscle"Naunyn-Schmiedeberg's Arch. Pharmacol.. 365. 56-66 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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