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. 1993 Aug;109(4):1232–1238. doi: 10.1111/j.1476-5381.1993.tb13754.x

Induction by endogenous noradrenaline of an alpha 1-adrenoceptor-mediated positive inotropic effect in rabbit papillary muscles.

Y Hattori 1, Y Takeda 1, H Nakaya 1, M Kanno 1
PMCID: PMC2175769  PMID: 8401934

Abstract

1. The possible involvement of alpha 1-adrenoceptors in the inotropic and electrophysiological responses to endogenous noradrenaline released by tyramine was examined in rabbit papillary muscles. 2. A concentration-dependent positive inotropic effect was produced by tyramine. This effect of tyramine was not observed in muscles from rabbits pretreated with reserpine. 3. The positive inotropic effect of tyramine was greatly inhibited by propranolol, but not altered by prazosin. However, when beta-adrenoceptors were blocked by pretreatment with propranolol, tyramine still produced a positive inotropic effect, an effect which was antagonized by prazosin. 4. Tyramine caused a decrease in action potential duration (APD) and an increase in action potential amplitude in a concentration-dependent manner. Isoprenaline also produced the same electrophysiological effects. These electrophysiological effects of both agents were inhibited by propranolol. 5. When beta-adrenoceptors were blocked by propranolol, the observed prazosin-sensitive positive inotropic effect of tyramine was not accompanied by any change in APD. In contrast, APD was markedly prolonged by alpha 1-adrenoceptor stimulation with phenylephrine in the presence of propranolol, in association with the positive inotropic effect. 6. It is concluded that in rabbit papillary muscles, endogenous noradrenaline causes a positive inotropic effect predominantly mediated by beta-adrenoceptors, but can still evoke a positive inotropic effect through alpha 1-adrenoceptors when beta-adrenoceptor stimulation is eliminated. This suggests that the alpha 1-adrenoceptor-mediated positive intropic mechanism(s) may be masked by simultaneous activation of beta-adrenoceptors. In addition, this study indicates that APD prolongation is not involved in the alpha 1-adrenoceptor-mediated inotropic responses to endogenous noradrenaline.

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Selected References

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  1. Aass H., Skomedal T., Osnes J. B. Demonstration of an alpha adrenoceptor-mediated inotropic effect of norepinephrine in rabbit papillary muscle. J Pharmacol Exp Ther. 1983 Aug;226(2):572–578. [PubMed] [Google Scholar]
  2. Alexander R. W., Williams L. T., Lefkowitz R. J. Identification of cardiac beta-adrenergic receptors by (minus) [3H]alprenolol binding. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1564–1568. doi: 10.1073/pnas.72.4.1564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Apkon M., Nerbonne J. M. Alpha 1-adrenergic agonists selectively suppress voltage-dependent K+ current in rat ventricular myocytes. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8756–8760. doi: 10.1073/pnas.85.22.8756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benfey B. G. Function of myocardial alpha-adrenoceptors. Life Sci. 1982 Jul 12;31(2):101–112. doi: 10.1016/0024-3205(82)90421-0. [DOI] [PubMed] [Google Scholar]
  5. Dukes I. D., Vaughan Williams E. M. Effects of selective alpha 1-, alpha 2-, beta 1-and beta 2-adrenoceptor stimulation on potentials and contractions in the rabbit heart. J Physiol. 1984 Oct;355:523–546. doi: 10.1113/jphysiol.1984.sp015436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ehrlich B. E., Watras J. Inositol 1,4,5-trisphosphate activates a channel from smooth muscle sarcoplasmic reticulum. Nature. 1988 Dec 8;336(6199):583–586. doi: 10.1038/336583a0. [DOI] [PubMed] [Google Scholar]
  7. Endoh M., Blinks J. R. Actions of sympathomimetic amines on the Ca2+ transients and contractions of rabbit myocardium: reciprocal changes in myofibrillar responsiveness to Ca2+ mediated through alpha- and beta-adrenoceptors. Circ Res. 1988 Feb;62(2):247–265. doi: 10.1161/01.res.62.2.247. [DOI] [PubMed] [Google Scholar]
  8. Endoh M., Hiramoto T., Ishihata A., Takanashi M., Inui J. Myocardial alpha 1-adrenoceptors mediate positive inotropic effect and changes in phosphatidylinositol metabolism. Species differences in receptor distribution and the intracellular coupling process in mammalian ventricular myocardium. Circ Res. 1991 May;68(5):1179–1190. doi: 10.1161/01.res.68.5.1179. [DOI] [PubMed] [Google Scholar]
  9. Endoh M., Schümann H. J., Krappitz N., Hillen B. alpha-Adrenoceptors mediating positive inotropic effects on the ventricular myocardium: some aspects of structure-activity relationship of sympathomimetic amines. Jpn J Pharmacol. 1976 Apr;26(2):179–190. doi: 10.1254/jjp.26.179. [DOI] [PubMed] [Google Scholar]
  10. Endou M., Hattori Y., Tohse N., Kanno M. Protein kinase C is not involved in alpha 1-adrenoceptor-mediated positive inotropic effect. Am J Physiol. 1991 Jan;260(1 Pt 2):H27–H36. doi: 10.1152/ajpheart.1991.260.1.H27. [DOI] [PubMed] [Google Scholar]
  11. Fedida D., Shimoni Y., Giles W. R. A novel effect of norepinephrine on cardiac cells is mediated by alpha 1-adrenoceptors. Am J Physiol. 1989 May;256(5 Pt 2):H1500–H1504. doi: 10.1152/ajpheart.1989.256.5.H1500. [DOI] [PubMed] [Google Scholar]
  12. Giotti A., Ledda F., Mannaioni P. F. Effects of noradrenaline and isoprenaline, in combination with - and -receptor blocking substances, on the action potential of cardiac Purkinje fibres. J Physiol. 1973 Feb;229(1):99–113. doi: 10.1113/jphysiol.1973.sp010129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Guse A. H., Berg I., Gercken G. Inhibition of alpha 1-adrenoceptor-mediated inositol phosphate accumulation in cultured cardiac myocytes by cyclic AMP-generating compounds. J Mol Cell Cardiol. 1991 Dec;23(12):1375–1382. doi: 10.1016/0022-2828(91)90184-n. [DOI] [PubMed] [Google Scholar]
  14. Harvey R. D., Hume J. R. Autonomic regulation of a chloride current in heart. Science. 1989 May 26;244(4907):983–985. doi: 10.1126/science.2543073. [DOI] [PubMed] [Google Scholar]
  15. Hattori Y., Endou M., Kanno M. Inhibition by 5-hydroxytryptamine of the beta adrenoceptor-mediated positive inotropic responses to catecholamines in rabbit papillary muscles: direct interaction with beta adrenoceptors. J Pharmacol Exp Ther. 1992 Jun;261(3):1160–1166. [PubMed] [Google Scholar]
  16. Hattori Y., Nakaya H., Endou M., Kanno M. Inotropic, electrophysiological and biochemical responses to histamine in rabbit papillary muscles: evidence for coexistence of H1- and H2-receptors. J Pharmacol Exp Ther. 1990 Apr;253(1):250–256. [PubMed] [Google Scholar]
  17. Jakob H., Nawrath H., Rupp J. Adrenoceptor-mediated changes of action potential and force of contraction in human isolated ventricular heart muscle. Br J Pharmacol. 1988 Jun;94(2):584–590. doi: 10.1111/j.1476-5381.1988.tb11564.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kameyama M., Hofmann F., Trautwein W. On the mechanism of beta-adrenergic regulation of the Ca channel in the guinea-pig heart. Pflugers Arch. 1985 Oct;405(3):285–293. doi: 10.1007/BF00582573. [DOI] [PubMed] [Google Scholar]
  19. Kass R. S., Wiegers S. E. The ionic basis of concentration-related effects of noradrenaline on the action potential of calf cardiac purkinje fibres. J Physiol. 1982 Jan;322:541–558. doi: 10.1113/jphysiol.1982.sp014054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kushida H., Hiramoto T., Satoh H., Endoh M. Phorbol ester does not mimic, but antagonizes the alpha-adrenoceptor-mediated positive inotropic effect in the rabbit papillary muscle. Naunyn Schmiedebergs Arch Pharmacol. 1988 Feb;337(2):169–176. doi: 10.1007/BF00169245. [DOI] [PubMed] [Google Scholar]
  21. Miura Y., Inui J. Multiple effects of alpha-adrenoceptor stimulation on the action potential of the rabbit atrium. Naunyn Schmiedebergs Arch Pharmacol. 1984 Jan;325(1):47–53. doi: 10.1007/BF00507053. [DOI] [PubMed] [Google Scholar]
  22. Movsesian M. A., Thomas A. P., Selak M., Williamson J. R. Inositol trisphosphate does not release Ca2+ from permeabilized cardiac myocytes and sarcoplasmic reticulum. FEBS Lett. 1985 Jun 17;185(2):328–332. doi: 10.1016/0014-5793(85)80932-7. [DOI] [PubMed] [Google Scholar]
  23. Mukherjee A., Haghani Z., Brady J., Bush L., McBride W., Buja L. M., Willerson J. T. Differences in myocardial alpha- and beta-adrenergic receptor numbers in different species. Am J Physiol. 1983 Dec;245(6):H957–H961. doi: 10.1152/ajpheart.1983.245.6.H957. [DOI] [PubMed] [Google Scholar]
  24. Nakaya H., Hattori Y., Tohse N., Shida S., Kanno M. Beta-adrenoceptor-mediated depolarization of the resting membrane in guinea-pig papillary muscles: changes in intracellular Na+, K+ and Cl- activities. Pflugers Arch. 1990 Oct;417(2):185–193. doi: 10.1007/BF00370698. [DOI] [PubMed] [Google Scholar]
  25. Nosek T. M., Williams M. F., Zeigler S. T., Godt R. E. Inositol trisphosphate enhances calcium release in skinned cardiac and skeletal muscle. Am J Physiol. 1986 May;250(5 Pt 1):C807–C811. doi: 10.1152/ajpcell.1986.250.5.C807. [DOI] [PubMed] [Google Scholar]
  26. Otani H., Otani H., Das D. K. Alpha 1-adrenoceptor-mediated phosphoinositide breakdown and inotropic response in rat left ventricular papillary muscles. Circ Res. 1988 Jan;62(1):8–17. doi: 10.1161/01.res.62.1.8. [DOI] [PubMed] [Google Scholar]
  27. Pappano A. J. Propranolol-insensitive effects of epinephrine on action potential repolarization in electrically driven atria of the guinea pig. J Pharmacol Exp Ther. 1971 Apr;177(1):85–95. [PubMed] [Google Scholar]
  28. Puceat M., Clement O., Lechene P., Pelosin J. M., Ventura-Clapier R., Vassort G. Neurohormonal control of calcium sensitivity of myofilaments in rat single heart cells. Circ Res. 1990 Aug;67(2):517–524. doi: 10.1161/01.res.67.2.517. [DOI] [PubMed] [Google Scholar]
  29. Schümann H. J., Endo M., Wagner J. Positive inotropic effects of phenylephrine in the isolated rabbit papillary muscle mediated both by alpha- and beta-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1974;284(2):133–148. doi: 10.1007/BF00501118. [DOI] [PubMed] [Google Scholar]
  30. Schümann H. J., Wagner J., Knorr A., Reidemeister J. C., Sadony V., Schramm G. Demonstration in human atrial preparations of alpha-adrenoceptors mediating positive inotropic effects. Naunyn Schmiedebergs Arch Pharmacol. 1978 May;302(3):333–336. doi: 10.1007/BF00508304. [DOI] [PubMed] [Google Scholar]
  31. Skomedal T., Aass H., Osnes J. B. Prazosin-sensitive component of the inotropic response to norepinephrine in rabbit heart. J Pharmacol Exp Ther. 1990 Feb;252(2):853–858. [PubMed] [Google Scholar]
  32. Skomedal T., Schiander I. G., Osnes J. B. Both alpha and beta adrenoceptor-mediated components contribute to final inotropic response to norepinephrine in rat heart. J Pharmacol Exp Ther. 1988 Dec;247(3):1204–1210. [PubMed] [Google Scholar]
  33. Tada M., Katz A. M. Phosphorylation of the sarcoplasmic reticulum and sarcolemma. Annu Rev Physiol. 1982;44:401–423. doi: 10.1146/annurev.ph.44.030182.002153. [DOI] [PubMed] [Google Scholar]
  34. Tohse N., Hattori Y., Nakaya H., Kanno M. Effects of alpha-adrenoceptor stimulation on electrophysiological properties and mechanics in rat papillary muscle. Gen Pharmacol. 1987;18(5):539–546. doi: 10.1016/0306-3623(87)90077-2. [DOI] [PubMed] [Google Scholar]
  35. Tohse N., Nakaya H., Hattori Y., Endou M., Kanno M. Inhibitory effect mediated by alpha 1-adrenoceptors on transient outward current in isolated rat ventricular cells. Pflugers Arch. 1990 Feb;415(5):575–581. doi: 10.1007/BF02583508. [DOI] [PubMed] [Google Scholar]
  36. Tsien R. W. Cyclic AMP and contractile activity in heart. Adv Cyclic Nucleotide Res. 1977;8:363–420. [PubMed] [Google Scholar]
  37. VAN ROSSUM J. M. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther. 1963;143:299–330. [PubMed] [Google Scholar]
  38. Wagner J., Schümann H. J., Knorr A., Rohm N., Reidemeister J. C. Stimulation by adrenaline and dopamine but not by noradrenaline of myocardial alpha-adrenoceptors mediating positive inotropic effects in human atrial preparations. Naunyn Schmiedebergs Arch Pharmacol. 1980 May;312(1):99–102. doi: 10.1007/BF00502581. [DOI] [PubMed] [Google Scholar]
  39. Walsh K. B., Kass R. S. Regulation of a heart potassium channel by protein kinase A and C. Science. 1988 Oct 7;242(4875):67–69. doi: 10.1126/science.2845575. [DOI] [PubMed] [Google Scholar]
  40. Williams R. S., Lefkowitz R. J. Alpha-adrenergic receptors in rat myocardium. Identification by binding of [3H]dihydroergocryptine. Circ Res. 1978 Nov;43(5):721–727. doi: 10.1161/01.res.43.5.721. [DOI] [PubMed] [Google Scholar]
  41. Yuan S. H., Sunahara F. A., Sen A. K. Tumor-promoting phorbol esters inhibit cardiac functions and induce redistribution of protein kinase C in perfused beating rat heart. Circ Res. 1987 Sep;61(3):372–378. doi: 10.1161/01.res.61.3.372. [DOI] [PubMed] [Google Scholar]

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