Differential Inotropic Effects of Endothelin-1, Angiotensin 2, and Phenylephrine Induced by Crosstalk With cAMP-Mediated Signaling Process in Dog Ventricular Myocardium

  • Chu Li
    Department of Cardiovascular Pharmacology, Yamagata University School of Medicine
  • Norota Ikuo
    Department of Cardiovascular Pharmacology, Yamagata University School of Medicine
  • Yomogida Shin-ichi
    Department of Cardiovascular Pharmacology, Yamagata University School of Medicine
  • Ishii Kuniaki
    Department of Cardiovascular Pharmacology, Yamagata University School of Medicine
  • Endoh Masao
    Department of Cardiovascular Pharmacology, Yamagata University School of Medicine

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タイトル別名
  • Differential Inotropic Effects of Endothelin-1, Angiotensin II, and Phenylephrine Induced by Crosstalk With cAMP-Mediated Signaling Process in Dog Ventricular Myocardium

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説明

Endothelin-1 (ET-1), angiotensin II (Ang II), and phenylephrine, an α1-adrenoceptor agonist, share the common signaling process, resulting in activation of Gq protein-coupled receptor (GqPCR) to activate the hydrolysis of phosphoinositide (PI). They do not elicit any inotropic effect in isolated dog ventricular muscle. In the presence of forskolin or IBMX (3-isobutyl-1-methylxanthine), ET-1 produced a dual effect, that is, a positive inotropic effect (PIE) and/or a negative inotropic effect (NIE) depending on concentrations of forskolin or IBMX present simultaneously with ET-1. Phenylephrine produced a definite PIE and Ang II induced a small and transient PIE in the presence of forskolin or IBMX, but they did not elicit a NIE. Facilitation of Ca2+ influx via L-type Ca2+ channel may play a crucial role in the crosstalk because GqPCR agonists produced, likewise a PIE in the presence of Bay k 8644. GqPCR agonists failed to induce a PIE in the presence of dihydroouabain or elevated [Ca2+]o. These findings indicate that the accumulation of cAMP or activation of L-type Ca2+ channels markedly modulates the inotropic response to GqPCR agonists in a manner that leads to a PIE in dog ventricular myocardium. In addition, ET-1, but not Ang II or phenylephrine, activates the signal transduction process that results in a NIE.<br>

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