Phosphatase inhibitor cantharidin blocks adenosine A1receptor anti-adrenergic effect in rat cardiac myocytes
- 1 January 2000
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 278 (1) , H1-H7
- https://doi.org/10.1152/ajpheart.2000.278.1.h1
Abstract
Experiments were performed to examine whether the protein phosphatase inhibitor cantharidin blocks the anti-adrenergic effect of adenosine A1receptor stimulation. In electrically stimulated adult rat ventricular myocytes loaded with the intracellular calcium concentration ([Ca2+]i) indicator fluo-3, isoproterenol (10 nM) increased systolic [Ca2+]iby 46%, increased twitch amplitude by 56%, and increased total cellular cAMP content by 140%. The adenosine A1receptor agonist 2-chloro- N6-cyclopentlyadenosine (CCPA) reduced isoproterenol-stimulated [Ca2+]iand contractility by 87 and 80%, respectively, but reduced cAMP content by only 18%. Cantharidin had no effects on myocyte [Ca2+]i, contractility, or cAMP in the absence or presence of isoproterenol but blocked the effects of CCPA on [Ca2+]iand contractility by ∼44%. Cantharidin had no effect on CCPA attenuation of isoproterenol-induced increases in cAMP. Pretreatment with CCPA also reduced the increase in contractile parameters produced by the direct cAMP-dependent protein kinase A (PKA) activator 8-bromocAMP. These results suggest that activation of protein phosphatases mediate, in part, the anti-adrenergic effect of adenosine A1receptor activation in ventricular myocardium.Keywords
This publication has 22 references indexed in Scilit:
- Contractility and Inhibition of Protein Phosphatases by CantharidinGeneral Pharmacology: The Vascular System, 1998
- Adenosine A1Receptor Stimulation Antagonizes the Negative Inotropic Effects of the PKC Activator DioctanoylglycerolJournal of Molecular and Cellular Cardiology, 1998
- Immunodetection of Phosphorylation Sites Gives New Insights into the Mechanisms Underlying Phospholamban Phosphorylation in the Intact HeartJournal of Biological Chemistry, 1996
- Adenosine A2 Receptor Occupancy Regulates Stimulated Neutrophil Function via Activation of a Serine/Threonine Protein PhosphataseJournal of Biological Chemistry, 1996
- Cantharidin Effects on Protein Phosphatases and the Phosphorylation State of Phosphoproteins in MiceToxicology and Applied Pharmacology, 1995
- 5′‐(N‐Ethylcarboxamido)adenosine Inhibits Ca2+ Influx and Activates a Protein Phosphatase in Bovine Adrenal Chromaffin CellsJournal of Neurochemistry, 1995
- Cantharidin, another natural toxin that inhibits the activity of serine/threonine protein phosphatases types 1 and 2AFEBS Letters, 1993
- Contractile properties of isolated porcine ventricular myocytesCardiovascular Research, 1993
- Increase of cyclic AMP in subcellular fractions of rat heart muscle after β-adrenergic stimulation: Prenalterol and isoprenaline caused different distribution of bound cyclic AMPJournal of Molecular and Cellular Cardiology, 1988
- Mechanism of adenosine inhibition of catecholamine-induced responses in heart.Circulation Research, 1983