Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1986 Apr;87(4):623–629. doi: 10.1111/j.1476-5381.1986.tb14578.x

Interaction of amrinone with endogenous adenosine in guinea-pig atria.

P Dorigo, I Maragno
PMCID: PMC1916808  PMID: 3708202

Abstract

In spontaneously beating atria from reserpine-treated guinea-pigs, amrinone (10 microM to 2 mM) induced a positive inotropic and chronotropic effect that was preceded by a transient reduction in contractile force and in frequency. Both the positive and negative effects were concentration-dependent. The inotropic action of amrinone was antagonized by low concentrations of 8-phenyltheophylline that compete with adenosine at R-receptors on plasma membrane without significantly influencing phosphodiesterase activity. Cumulative concentrations of amrinone (1 mM) antagonized the reduction of rate of contraction and amplitude induced by dipyridamole 1 microM in spontaneously beating atria and restored the maximum contractile effect reached in the absence of dipyridamole. In spontaneously beating preparations incubated in the presence of adenosine deaminase (1 u ml-1), amrinone lost its positive effects on the atria and only reduction of rate and contractile force was evident. Both effects were antagonized by scopolamine 1 mM thus indicating their cholinergic nature. Adenosine at 0.1 microM and 0.5 microM significantly inhibited the inotropic effect induced by amrinone (0.03 to 3 mM) and the concentration-effect curves of amrinone obtained in the absence and presence of adenosine clearly indicate a competitive antagonism between the two drugs. Thus the contractile activity of amrinone in spontaneously beating atria from reserpine-treated guinea-pigs originates from a displacement of adenosine from its R-receptor sites in the cardiac cell.

Full text

PDF
623

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alousi A. A., Farah A. E., Lesher G. Y., Opalka C. J., Jr Cardiotonic activity of amrinone--Win 40680 [5-amino-3,4'-bipyridine-6(1H)-one]. Circ Res. 1979 Nov;45(5):666–677. doi: 10.1161/01.res.45.5.666. [DOI] [PubMed] [Google Scholar]
  2. Azari J., Huxtable R. J. Differential effects of amrinone on contractility and taurine influx in rat and guinea pig hearts. Eur J Pharmacol. 1980 Oct 31;67(4):347–353. doi: 10.1016/0014-2999(80)90175-2. [DOI] [PubMed] [Google Scholar]
  3. Benotti J. R., Grossman W., Braunwald E., Davolos D. D., Alousi A. A. Hemodynamic assessment of amrinone. A new inotropic agent. N Engl J Med. 1978 Dec 21;299(25):1373–1377. doi: 10.1056/NEJM197812212992501. [DOI] [PubMed] [Google Scholar]
  4. Binah O., Legato M. J., Danilo P., Jr, Rosen M. R. Developmental changes in the cardiac effects of amrinone in the dog. Circ Res. 1983 Jun;52(6):747–752. doi: 10.1161/01.res.52.6.747. [DOI] [PubMed] [Google Scholar]
  5. Bruns R. F. Adenosine antagonism by purines, pteridines and benzopteridines in human fibroblasts. Biochem Pharmacol. 1981 Feb 15;30(4):325–333. doi: 10.1016/0006-2952(81)90062-9. [DOI] [PubMed] [Google Scholar]
  6. Dunwiddie T. V., Hoffer B. J., Fredholm B. B. Alkylxanthines elevate hippocampal excitability. Evidence for a role of endogenous adenosine. Naunyn Schmiedebergs Arch Pharmacol. 1981 Jul;316(4):326–330. doi: 10.1007/BF00501365. [DOI] [PubMed] [Google Scholar]
  7. Endoh M., Yamashita S., Taira N. Positive inotropic effect of amrinone in relation to cyclic nucleotide metabolism in the canine ventricular muscle. J Pharmacol Exp Ther. 1982 Jun;221(3):775–783. [PubMed] [Google Scholar]
  8. Gaide M. S., Fitterman W. S., Wiggins J. R., Myerburg R. J., Cameron J. S., Bassett A. L. Amrinone relaxes potassium-induced contracture of failing right ventricular muscle of cats. J Cardiovasc Pharmacol. 1983 Mar-Apr;5(2):335–340. doi: 10.1097/00005344-198303000-00028. [DOI] [PubMed] [Google Scholar]
  9. Grossman W., McLaurin L. P., Rolett E. L. Alterations in left ventricular relaxation and diastolic compliance in congestive cardiomyopathy. Cardiovasc Res. 1979 Sep;13(9):514–522. doi: 10.1093/cvr/13.9.514. [DOI] [PubMed] [Google Scholar]
  10. Honerjäger P., Schäfer-Korting M., Reiter M. Involvement of cyclic AMP in the direct inotropic action of amrinone. Biochemical and functional evidence. Naunyn Schmiedebergs Arch Pharmacol. 1981 Dec;318(2):112–120. doi: 10.1007/BF00508835. [DOI] [PubMed] [Google Scholar]
  11. Kariya T., Wille L. J., Dage R. C. Biochemical studies on the mechanism of cardiotonic activity of MDL 17,043. J Cardiovasc Pharmacol. 1982 May-Jun;4(3):509–514. doi: 10.1097/00005344-198205000-00024. [DOI] [PubMed] [Google Scholar]
  12. Klein N. A., Siskind S. J., Frishman W. H., Sonnenblick E. H., LeJemtel T. H. Hemodynamic comparison of intravenous amrinone and dobutamine in patients with chronic congestive heart failure. Am J Cardiol. 1981 Jul;48(1):170–175. doi: 10.1016/0002-9149(81)90587-7. [DOI] [PubMed] [Google Scholar]
  13. LeJemtel T. H., Keung E., Sonnenblick E. H., Ribner H. S., Matsumoto M., Davis R., Schwartz W., Alousi A. A., Davolos D. Amrinone: a new non-glycosidic, non-adrenergic cardiotonic agent effective in the treatment of intractable myocardial failure in man. Circulation. 1979 Jun;59(6):1098–1104. doi: 10.1161/01.cir.59.6.1098. [DOI] [PubMed] [Google Scholar]
  14. Meisheri K. D., Palmer R. F., Van Breemen C. The effects of amrinone on contractility, Ca2+ uptake and cAMP in smooth muscle. Eur J Pharmacol. 1980 Jan 25;61(2):159–165. doi: 10.1016/0014-2999(80)90158-2. [DOI] [PubMed] [Google Scholar]
  15. Rendig S. V., Amsterdam E. A. Positive inotropic action of amrinone: effect of elevated external Ca2+. J Cardiovasc Pharmacol. 1984 Mar-Apr;6(2):293–299. doi: 10.1097/00005344-198403000-00014. [DOI] [PubMed] [Google Scholar]
  16. Scotini E., Carpenedo F., Fassina G. New derivatives of methyl-xanthines: effect of thiocaffeine thiotheophylline and 8-phenyltheophylline on lipolysis and on phosphodiesterase activities. Pharmacol Res Commun. 1983 Feb;15(2):131–143. doi: 10.1016/s0031-6989(83)80055-1. [DOI] [PubMed] [Google Scholar]
  17. Seitelberger R., Schütz W., Schlappack O., Raberger G. Evidence against the adenosine-catecholamine antagonism under in vivo conditions. Naunyn Schmiedebergs Arch Pharmacol. 1984 Mar;325(3):234–239. doi: 10.1007/BF00495949. [DOI] [PubMed] [Google Scholar]
  18. Siegl P. K., Morgan G., Sweet C. S. Responses to amrinone in isolated cardiac muscles from cat, rabbit, and guinea pig. J Cardiovasc Pharmacol. 1984 Mar-Apr;6(2):281–287. doi: 10.1097/00005344-198403000-00012. [DOI] [PubMed] [Google Scholar]
  19. Smellie F. W., Davis C. W., Daly J. W., Wells J. N. Alkylxanthines: inhibition of adenosine-elicited accumulation of cyclic AMP in brain slices and of brain phosphodiesterase activity. Life Sci. 1979 Jun 25;24(26):2475–2482. doi: 10.1016/0024-3205(79)90458-2. [DOI] [PubMed] [Google Scholar]
  20. Temma K., Akera T., Brody T. M. Hydroxylated chlorpromazine metabolites: positive inotropic action and the release of catecholamines. Mol Pharmacol. 1977 Nov;13(6):1076–1085. [PubMed] [Google Scholar]
  21. Toda N., Nakajima M., Nishimura K., Miyazaki M. Responses of isolated dog arteries to amrinone. Cardiovasc Res. 1984 Mar;18(3):174–182. doi: 10.1093/cvr/18.3.174. [DOI] [PubMed] [Google Scholar]
  22. Ward A., Brogden R. N., Heel R. C., Speight T. M., Avery G. S. Amrinone. A preliminary review of its pharmacological properties and therapeutic use. Drugs. 1983 Dec;26(6):468–502. doi: 10.2165/00003495-198326060-00002. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES