Effects of papaverine and its interaction with isoprenaline and carbachol on the contractile force and cyclic nucleotide levels of the canine ventricular myocardium
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Papaverine (3×10−5 M) induced a positive inotropic action and increased the cyclic AMP level in the majority of preparations. Ventricular muscles isolated from certain dogs showed only a negative inotropic response to papaverine. As a whole, a significant correlation was found between the tension developed and the cyclic AMP level after the administration of papaverine. The cyclic GMP level was not changed or decreased by papaverine.
The positive inotropic action of papaverine and elevation of the cyclic AMP level in response to papaverine were not inhibited by a β-adrenoceptor blocking drug, pindolol (3×10−8 M), indicating that these effects are not caused by catecholamine release.
In muscles, in which papaverine failed to cause the positive inotropic action, contractile as well as cyclic AMP responses to isoprenaline were significantly enhanced by papaverine.
Carbachol (3×10−6M) diminished the positive inotropic actions of isoprenaline and papaverine, abolished the accumulation of cyclic AMP produced by these agents, and increased significantly the cyclic GMP level. The elevation of cyclic GMP level by carbachol in the presence of papaverine was especially marked and amounted to 4-fold the corresponding control value. These results indicate that papaverine inhibits the break down of the intracellular cyclic AMP and GMP in the intact myocardial cells and may thereby interact functionally with the autonomic nervous system.
Key wordsPapaverine Isoprenaline Carbachol Cyclic AMP Cyclic GMP Ventricular contraction
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- Blinks, J. R.: Field stimulation as a means of effecting the graded release of autonomic transmitters in isolated heart muscle. J. Pharmacol. Exp. Ther. 151, 221–235 (1966)Google Scholar
- Cailla, H. L., Racine-Weisbuch, M. S., Delaage, M. A.: Adenosine 3′,5′ cyclic monophosphate assay at 10−15mole level. Anal. Biochem. 56, 394–407 (1973)Google Scholar
- Cheung, W. Y., Williamson, J. R.: Kinetics of cyclic adenosine monophosphate changes in rat heart following epinephrine administration. Nature 207, 979–981 (1965)Google Scholar
- Dobson, J. G. Jr., Ross, J., Jr., Mayer, S. E.: The role of cyclic adenosine 3′,5′-monophosphate and calcium in the regulation of contractility and glycogen phosphorylase activity in guinea pig papillary muscle. Circ. Res. 39, 388–395 (1976)Google Scholar
- Endoh, M., Schümann, H. J.: Effects of papaverine on isolated rabbit papillary muscle. Eur. J. Pharmacol. 30, 213–220 (1975)Google Scholar
- Endoh, M., Brodde, O.-E., Schümann, H. J.: Accumulation of cAMP and positive inotropic effect evoked by isoproterenol under the graded inhibition of phosphodiesterase by papaverine in the isolated rabbit papillary muscle. J. Mol. Cell. Cardiol. 7, 703–711 (1975)Google Scholar
- Gardner, R. M., Allen, D. O.: Regulation of cyclic nucleotide levels and glycogen phosphorylase activity by acetylcholine and epinephrine in perfused rat hearts. J. Pharmacol. Exp. Ther. 198, 412–419 (1976)Google Scholar
- George, W. J., Polson, J. B., O'Toole, A. G., Goldberg, N. D.: Elevation of guanosine 3′,5′-cyclic phosphate in rat heart after perfusion with acetylcholine. Proc. Natl. Acad. Sci. USA 66, 398–403 (1970)Google Scholar
- George, W. J., Wilkerson, R. D., Kadowitz, P. J.: Influence of acetylcholine on contractile force and cyclic nucleotide levels in the isolated perfused rat heart.J. Pharmacol. Exp. Ther. 184, 228–235 (1973)Google Scholar
- Henry, P. D., Sobel, B. E.: Disparate effects of papaverine on cyclic AMP and contractility. Circulation, Suppl. 46, II-120 (1972)Google Scholar
- Henry, P. D., Dobson, J. G., Jr., Sobel, B. E.: Dissociations between changes in myocardial cyclic adenosine monophosphate and contractility. Circ. Res. 36, 392–400 (1975)Google Scholar
- Honma, M., Satoh, T., Takezawa, J., Ui, M.: An ultrasensitive method for the simultaneous determination of cyclic AMP and cyclic GMP in small-volume samples from blood and tissue. Biochem. Med. 18, 257–273 (1977)Google Scholar
- Kukovetz, W. R., Pöch, G., Wurm, A.: Effect of catecholamines, histamine and oxyfedrine on isotonic contraction and cyclic AMP in the guinea-pig heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 403–424 (1973)Google Scholar
- Kukovetz, W. R., Pöch, G., Wurm, A.: Quantitative relations between cyclic AMP and contraction as affected by stimulators of adenylate cyclase and inhibitors of phosphodiesterase. Adv. Cycl. Nucleot. Res. Vol. 5(G. I. Drummond, P. Greengard, and G. A. Robison, eds.), pp. 395–414. New York: Raven Press 1975Google Scholar
- Kuo, J.-F., Lee, T.-P., Reyes, P. L., Walton, K. G., Donnelly, T. E., jr., Greengard, P.: Cyclic nucleotide-dependent protein kinases. X. An assay method for the measurement of guanosine 3′,5′-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain. J. Biol. Chem. 247, 16–22 (1972)Google Scholar
- Lugnier, C., Stoclet, J.-C.: Inhibition by papaverine of cGMP and cAMP phosphodiesterases from the rat heart. Biochem. Pharmacol. 23, 3071–3074 (1974)Google Scholar
- Meester, W. D., Hardman, H. F.: Blockade of the positive inotropic actions of epinephrine and theophylline by acetylcholine. J. Pharmacol. Exp. Ther. 158, 241–247 (1967)Google Scholar
- Meinertz, T., Nawrath, H., Scholz, H., Winter, K.: Effect of DB-c-AMP on mechanical characteristics of ventricular and atrial preparations of several mammalian species. Naunyn-Schmiedeberg's Arch. Pharmacol. 282, 143–153 (1974)Google Scholar
- Murad, F., Chi, Y.-M., Rall, T. W., Sutherland, E. W.: Adenyl cyclase. III. The effect of catecholamines and choline esters on the formation of adenosine 3′,5′-phosphate by preparations from cardiac muscle and liver. J. Biol. Chem. 237, 1233–1238 (1962)Google Scholar
- Nawrath, H.: Cyclic AMP and cyclic GMP may play opposing roles in influencing force of contraction in mammalian myocardium. Nature 262, 509–511 (1976)Google Scholar
- Nawrath, H., Meinertz, T.: Electrical and mechanical activity of mammalian heart muscle fibres treated with papaverine. Interaction with isoprenaline and dibutyryl cyclic AMP. Naunyn-Schmiedeberg's Arch. Pharmacol. 299, 253–258 (1977)Google Scholar
- Pöch, G., Kukovetz, W. R.: Papaverine-induced inhibition of phosphodiesterase activity in various mammalian tissues. Life Sci. 10, 133–144 (1971)Google Scholar
- Reinhardt, D., Roggenbach, W., Brodde, O.-E., Schümann, H. J.: Influence of papaverine and isoprenaline on contractility and cyclic AMP level of left guinea-pig atria at different rates of beat. Naunyn-Schmiedeberg's Arch. Pharmacol. 299, 9–15 (1977)Google Scholar
- Robison, G. A., Butcher, R. W., Øye, I., Morgan, H. E., Sutherland, E. W.: The effect of epinephrine on adenosine 3′,5′-phosphate levels in the isolated perfused rat heart. Mol. Pharmacol. 1, 168–177 (1965)Google Scholar
- Schneider, J. A., Brooker, G., Sperelakis, N.: Papaverine blockade of an inward slow Ca++-current in guinea-pig heart. J. Mol. Cell. Cardiol. 7, 867–876 (1975)Google Scholar
- Schümann, H. J., Endoh, M., Brodde, O.-E.: The time course of the effects of β-and α-adrenoceptor stimulation by isoprenaline and methoxamine on the contractile force and cAMP level of the isolated rabbit papillary muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 289, 291–302 (1975)Google Scholar
- Sutherland, E. W., Robison, G. A., Butcher, R. W.: Some aspects of the biological role of adenosine 3′,5′-monophosphate (cyclic AMP). Circulation 37, 279–306 (1968)Google Scholar
- Watanabe, A. M., Besch, H. R., Jr.: Interaction between cyclic adenosine monophosphate and cyclic guanosine monophosphate in guinea pig ventricular myocardium. Circ. Res. 37, 309–317 (1975)Google Scholar