Temporal dissociation between the negative inotropism and the increase in cyclic GMP level induced by choline esters in spontaneously beating rat atria preparations1

The effects of acetylcholine and carbacholine on cyclic GMP levels and contraction amplitude were investigated simultaneously in spontaneously beating rat atria preparations. Both drugs at the concentrations of 5times10^--⁷ M or higher produced a very rapid decline of amplitude. However, the cyclic GMP level was not elevated earlier than 5 s later, when the amplitude was already reduced to 50% of the initial value. Concentrations of acetylcholine below 5times 10^--⁷ M were not able to affect the cyclic GMP level, although they reduced the contractility significantly. Acetylcholine had no effect on the cyclic AMP level. The data demonstrate that cyclic GMP does not mediate the negative inotropic effect of choline esters in rat atria preparations.