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Differential Inhibition by the Phosphatase Inhibitor Cantharidin of the Anti-adrenergic Effect of Endothelin-1 and Carbachol in the Canine Ventricular Myocardium

  • Chapter
Pathophysiology of Cardiovascular Disease

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 10))

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Summary

Endothelin-1 (ET-1) and the muscarinic agonist carbachol do not affect the basal force of contraction, but induce a pronounced negative inotropic effect in the presence of β-adrenoceptor stimulation in the canine ventricular myocardium. We studied the influence of the phosphatase inhibitor cantharidin on the negative inotropic effect of ET-1 and carbachol in isolated canine right ventricular trabeculae and single ventricular myocytes. In the presence of 100 nM norepinephrine (NE), 10nM ET-1 and 30 nM carbachol induced a negative inotropic effect of an identical extent. Cantharidin at 10 μM did not affect the basal force of contraction and the positive inotropic effect of NE mediated by β-adrenoceptor stimulation. Cantharidin (10 μM) markedly attenuated the negative inotropic effect of ET-1, but it did not affect the negative inotropic effect of carbachol. At 30 μM, cantharidin induced a positive inotropic effect and enhanced the positive inotropic effect of NE. Cantharidin (30 μM) suppressed significantly the negative inotropic effect of carbachol (30 nM and 100 nM). In canine single ventricular myocytes, ET-1 (10nM) or carbachol (30nM) did not affect the baseline level of cell shortening and the amplitude of intracellular Ca2+ transients, while they inhibited the NE (30 μM)-induced increases in cell shortening and Ca2+ transients. Cantharidin (10 μM) attenuated the inhibitory action of ET-1, but did not affect the effects of carbachol in the presence of NE. These results indicate that the activation of phosphatase that is susceptible to cantharidin is involved in the negative inotropic effect of both ET-1 and carbachol. The extent of contribution of phosphatase activation appears to be greater in the ET-1-induced negative inotropic effect than in the effect of the muscarinic receptor agonist carbachol in the canine ventricular myocardium.

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Authors and Affiliations

  1. Department of Pharmacology, Yamagata University School of Medicine, Yamagata, 990-9585, Japan

    Masao Endoh, Li Chu, Ikuo Norota & Kuniaki Ishii

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  1. Masao Endoh
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  2. Li Chu
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  3. Ikuo Norota
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  4. Kuniaki Ishii
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Correspondence to Masao Endoh .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director) (Distinguished Professor and Director)

  2. Philipps University of Marburg, Marburg, Germany

    Heinz Rupp PhD (Professor of Medicine) (Professor of Medicine)

  3. Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Aubie Angel MD (Professor of Internal Medicine) (Professor of Internal Medicine)

  4. Division of Stroke & Vascular Disease St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Grant N. Pierce PhD, FACC (Professor & Director) (Professor & Director)

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Endoh, M., Chu, L., Norota, I., Ishii, K. (2004). Differential Inhibition by the Phosphatase Inhibitor Cantharidin of the Anti-adrenergic Effect of Endothelin-1 and Carbachol in the Canine Ventricular Myocardium. In: Dhalla, N.S., Rupp, H., Angel, A., Pierce, G.N. (eds) Pathophysiology of Cardiovascular Disease. Progress in Experimental Cardiology, vol 10. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0453-5_11

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  • DOI: https://doi.org/10.1007/978-1-4615-0453-5_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5084-2

  • Online ISBN: 978-1-4615-0453-5

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