Summary
The effects of cyclic 3′,5′-AMP and of two acylated derivatives, dibutyryl (DBA) and dihexanoyl-3′,5′-AMP (DHA) were investigated in isolated perfused hearts of guinea pigs, rats and rabbits.
In guinea pig hearts, DBA (Ca- and Na-salt) and DHA-Na in high doses (10 μmoles) produced strong and long lasting increases in the rate and amplitude of contractions, coronary flow, and moderate increases in phosphorylase activity in the majority of experiments. The positive ino- and chronotropic effects occured 3–5 min after injection of the drug, mostly in a fluctuating manner with several maxima. Theophylline augmented the effects of DBA-Na and revealed positive inotropic actions of non substituted 3′,5′-AMP.
In rat hearts, similar, but more pronounced and dose-dependent effects were observed after 1, 5 and 10 μmoles DBA-Na. Propranolol (50 μg) did not block the action of 10 μmoles DBA-Na. Non substituted 3′,5′-AMP, 5′-AMP and ATP in doses of 10 μmoles had no significant positive inotropic effects.
In rabbit hearts, DBA-Na (50 μmoles) produced moderate, non fluctuating rises in the amplitude of contraction.
The results provide evidence that under certain conditions cyclic 3′, 5′-AMP itself, like its acylated derivatives DBA and DHA, may produce strong and direct positive inotropic and chronotropic effects in the heart. These findings support the view that cyclic 3′,5′-AMP is the cellular mediator of the cardiostimulant actions of substances that increase its rate of production in the myocardial cell.
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The excellent technical help of Mrs. Vera Bauer is gratefully acknowledged by the authors.
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Kukovetz, W.R., Pöch, G. Cardiostimulatory effects of cyclic 3′,5′-adenosine monophosphate and its acylated derivatives. Naunyn-Schmiedebergs Arch. Pharmak. 266, 236–254 (1970). https://doi.org/10.1007/BF00997285
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DOI: https://doi.org/10.1007/BF00997285