Dibutyryl cyclic AMP exerts positive inotropic and chronotropic effects by entering the cell, whereas exogenous cyclic AMP acts extracellularly to produce negative inotropic and chronotropic effects.
Using the canine heart-lung preparation supported by a donor dog and the isolated right and left atrial preparations of the guinea-pig and the rat, the cardiac actions of dibutyryl cyclic AMP were studied and compared with those of cyclic. AMP. Dibutyryl cyclic AMP produced positive inotropic and chronotropic effects associated with an increase in the coronary flow, while cyclic AMP produced negative inotropic and chronotropic effects, together with an increase in the coronary flow. Propranolol did not alter the effects of dibutyryl cyclic AMP. The negative inotropic and chronotropic effect of cyclic AMP was antagonized by aminophylline, while the positive inotropic and chronotropic effect of dibutyryl cyclic AMP was potentiated by this compound. Whereas the coronary flow increase by dibutyryl cyclic AMP was associated with an increase in the myocardial oxygen consumption, there was no increase in the myocardial oxygen consumption after cyclic AMP. It is concluded that dibutyryl cyclic AMP passed the surface membrane and exerted its effect after having been converted to cyclic AMP within the cell. Cyclic AMP was presumed to remain outside the cell and produce its effect in the same way as adenine nucleotides and adenosine produce their effect.
Imai et al. (1974) studied this question.