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Logo of jphysiolThe Journal of Physiology SiteMembershipSubmissionJ Physiol
J Physiol. Aug 1976; 260(1): 117–141.
PMCID: PMC1309080

Inotropic effect of cyclic AMP in calf ventricular muscle studied by a cut end method.

Abstract

1. Cyclic AMP was introduced into ventricular muscle by a cut-end method. Trabecular bundles were pulled through a partition which divided the preparation into a loading region and a test region. The loading region was exposed to Ca-free solution, cut transversely near the partition, and then briefly exposed to cyclic AMP. The test region was continually superfused with Tyrode soltuion. 2. In preliminary experiments, cell-to-cell movements were studied in long bundles by including [3H]cyclic AMP in the loading procedure and allowing redistribution to occur. After suitable test periods, the bundles were removed, frozen, and sliced into segments. Segment radioactivity was plotted against distance and fitted by a theoretical diffusion curve. 3. The results showed longitudinal redistribution of label over many cell lengths with an average effective diffusivity of 8 X 10(-7) cm2/sec. This value did not appear sensitive to the length of the test period or to the presence of a phosphodiesterase inhibitor. 4. The metabolic fate of cyclic AMP introduced by the cut-end method was determined by chromatographic separation of [3H]cyclic AMP and its break-down products. Most of the cyclic AMP was metabolized, but the results suggest that cell-to-cell movements of cyclic AMP contribute to the overall redistribution of label. 5. The cut-end method was used to study the influence of cyclic AMP on the contractile activity in the test region. Introduction of cyclic AMP evoked a delayed increase in twitch tension, about 25% above control. The inotropic effect peaked about 50 min after the end of the loading procedure, a delay which seemed compatible with slow longitudinal diffusion into the test region. 6. In control experiments, the cut-end procedure was repeated with 5'AMP (the immediate break-down product of cyclic AMP) instead of cyclic AMP. No delayed increase in twitch tension was observed. 7. Introduction of dibutyryl cyclic AMP increased twitch amplitude by 130%, with a delayed time course similar to that found for cyclic AMP. 8. The results using the cut-end procedure provide new evidence that cyclic AMP helps mediate adrenergic effects on the strength of contraction.

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Selected References

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  • Borasio PG, Vassalle M. Dibutyryl cyclic AMP and potassium transport in cardiac Purkinje fibers. Am J Physiol. 1974 May;226(5):1232–1237. [PubMed]
  • Summer D, Manning RT. Crystallization of arginase from normal and cirrhotic human liver. Nature. 1965 Jul 3;207(992):79–80. [PubMed]
  • Drummond GI, Hemmings S, Warneboldt RB. Uptake and catabolism of N6, 2'-O-dibutyryl cyclic AMP by the perfused heart. Life Sci. 1974 Jul 15;15(2):319–328. [PubMed]
  • Entman ML. The role of cyclic AMP in the modulation of cardiac contractility. Adv Cyclic Nucleotide Res. 1974;4(0):163–193. [PubMed]
  • FURCHGOTT RF, LEE KS. High energy phosphates and the force of contraction of cardiac muscle. Circulation. 1961 Aug;24:416–432. [PubMed]
  • Hilz H, Tarnowski W. Opposite effects of cyclic AMP and its dibutyryl derivative on glycogen levels in HeLa cells. Biochem Biophys Res Commun. 1970 Aug 24;40(4):973–981. [PubMed]
  • Imanaga I. Cell-to-cell diffusion of procion yellow in sheep and calf Purkinje fibers. J Membr Biol. 1974;16(4):381–388. [PubMed]
  • KELLY JJ, Jr, HOFFMAN BF. Mechanical activity of rat papillary muscle. Am J Physiol. 1960 Jul;199:157–162. [PubMed]
  • Kjekshus JK, Henry PD, Sobel BE. Activation of phosphorylase by cyclic AMP without augmentation of contractility in perfused guinea pig heart. Circ Res. 1971 Nov;29(5):468–478. [PubMed]
  • Kline RL, Buckley JP. In vitro myocardial effects of 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (Ro 7-2956). J Pharmacol Exp Ther. 1972 Sep;182(3):399–408. [PubMed]
  • Kukovetz WR, Pöch G. Cardiostimulatory effects of cyclic 3',5'-adenosine monophosphate and its acylated derivatives. Naunyn Schmiedebergs Arch Pharmakol. 1970;266(3):236–254. [PubMed]
  • Kuo JF, Lee TP, Reyes PL, Walton KG, Donnelly TE, Jr, Greengard P. Cyclic nucleotide-dependent protein kinases. X. An assay method for the measurement of quanosine 3',5'-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain. J Biol Chem. 1972 Jan 10;247(1):16–22. [PubMed]
  • Langslet A, Oye I. The role of cyclic 3'5'-AMP in the cardiac response to adrenaline. Eur J Pharmacol. 1970 Oct;12(2):137–144. [PubMed]
  • Meinertz T, Nawrath H, Scholz H. Influence of cyclization and acyl substitution on the inotropic effects of adenine nucleotides. Naunyn Schmiedebergs Arch Pharmacol. 1973;278(2):165–178. [PubMed]
  • PAGE E. Cat heart muscle in vitro. III. The extracellular space. J Gen Physiol. 1962 Nov;46:201–213. [PMC free article] [PubMed]
  • RALL TW, WEST TC. The potentiation of cardiac inotropic responses to norepinephrine by theophylline. J Pharmacol Exp Ther. 1963 Mar;139:269–274. [PubMed]
  • Reuter H. Localization of beta adrenergic receptors, and effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle. J Physiol. 1974 Oct;242(2):429–451. [PMC free article] [PubMed]
  • Robison GA, Butcher RW, Oye I, Morgan HE, Sutherland EW. The effect of epinephrine on adenosine 3', 5'-phosphate levels in the isolated perfused rat heart. Mol Pharmacol. 1965 Sep;1(2):168–177. [PubMed]
  • Skelton CL, Levey GS, Epstein SE. Positive inotropic effects of dibutyryl cyclic adenosine 3',5'-monophosphate. Circ Res. 1970 Jan;26(1):35–43. [PubMed]
  • Sobel BE, Mayer SE. Cyclic adenosine monophosphate and cardiac contractility. Circ Res. 1973 Apr;32(4):407–414. [PubMed]
  • SONNENBLICK EH. Force-velocity relations in mammalian heart muscle. Am J Physiol. 1962 May;202:931–939. [PubMed]
  • SUTHERLAND EW, RALL TW. Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles. J Biol Chem. 1958 Jun;232(2):1077–1091. [PubMed]
  • Tsien RW. Adrenaline-like effects of intracellular iontophoresis of cyclic AMP in cardiac Purkinje fibres. Nat New Biol. 1973 Sep 26;245(143):120–122. [PubMed]
  • Tsien RW, Weingart R. Proceedings: Cyclic AMP: cell-to-cell movement and inotropic effect in ventricular muscle, studied by a cut-end method. J Physiol. 1974 Oct;242(2):95P–96P. [PubMed]
  • Weidmann S. The diffusion of radiopotassium across intercalated disks of mammalian cardiac muscle. J Physiol. 1966 Nov;187(2):323–342. [PMC free article] [PubMed]
  • Weidmann S. Electrical constants of trabecular muscle from mammalian heart. J Physiol. 1970 Nov;210(4):1041–1054. [PMC free article] [PubMed]
  • Weingart R. The permeability to tetraethylammonium ions of the surface membrane and the intercalated disks of sheep and calf myocardium. J Physiol. 1974 Aug;240(3):741–762. [PMC free article] [PubMed]
  • Yamasaki Y, Fujiwara M, Toda N. Effects of intracellularly applied cyclic 3',5'-adenosine monophosphate and dibutyryl cyclic 3',5'-adenosine monophosphate on the electrical activity of sinoatrial nodal cells of the rabbit. J Pharmacol Exp Ther. 1974 Jul;190(1):15–20. [PubMed]

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