Antagonism by guanosine 3',5'-cyclic monophosphate derivatives against the action of adrenaline on the automaticity of isolated rat heart muscle cells in culture.

Spontaneously and rhythmically beating single cells from the ventricles of new-born rats were cultured on coverslips for 3 to 4 days and transferred to a small perfusion chamber for photoelectric recording of their contractions. The cells responded to 3 - 10(-7) M adrenaline with a pronounced increase and to 1.7 - 10(-5) M carbamylcholine with a mode-rate decrease in the rate of beat. Carbamylcholine nearly abolished the beat-accelerating effect of adrenaline. 8-Bromo cyclic GMP and N2-2'-O-'DIBUTYRYL CYCLIC GMP, in concentrations of 4.2 to 8.4 - 10(-4) M, exerted only very slight depressant effects on the basal rate of beat, but strongly antagonized, and in the majority of experiments with 8-bromo cyclic GMP completely suppressed, the positive chronotropic action of adrenaline. Cyclic GMP, 5'-GMP, and 5'-guanylylimidodiphosphate were without effect. 8-Bromo cyclic AMP caused a marked acceleration of beating. In view of the mediator roles that cyclic AMP and cyclic GMP have been assigned in the cardiac actions of beta-adrenergic and of cholinergic agents, respectively, the present results may be interpreted as being indicative of an adrenergic-cholinergic antagonism at the level of these two cyclic nucleotides.