Paradoxical Effects of Calcium-Glucagon Interaction on Cardiac Muscle Contractility of Isolated Guinea Pig Atria

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Abstract
The interrelationships of Ca and glucagon, and Ca and Isuprel were investigated in spontaneous and paced isolated guinea pig atria. Positive force responses with glucagon were in part both frequency and [Ca+2]o-dependent. Negative inotropic responses were observed with high concentrations of glucagon (5.0 .mu.g/ml) and Ca (10.0 mM). Persistence of a positive inotropic response of the atria to Isuprel (1.0 .mu.g/ml) and high [Ca+2]o (10 mM) was seen. Catecholamines stimulate c[cyclic]AMP production in guinea pig atria while glucagon may not. The negative inotropism produced via Ca-glucagon interaction is consistent with the known inhibitory action of high Ca concentrations on adenylate cyclase and stimulation of phosphodiesterase. It is hyposthesized that since glucagon does not activate cAMP in this tissue then the combined action of high Ca and glucagon leads to degeneration of contractility; with Isuprel and high Ca, atrial contractility is maintained via Isuprel''s cAMP activation.