The interrelationships of calcium and glucagon, and calcium 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 μg/ml) and calcium (10.0 ms). Persistence of a positive inotropic response of the atria to Isuprel (1.0 μg/ml) and high [Ca+2]o (10 mM) was seen. Catecholamines stimulate c-AMP production in guinea pig atria while glucagon may not. The negative inotropism produced via calcium-glucagon interaction is consistent with the known inhibitory action of high calcium concentrations on adenylyl cyclase and stimulation of phosphodiesterase. It is hypothesized that since glucagon does not activate c-AMP in this tissue then the combined action of high calcium and glucagon leads to degeneration of contractility; with Isuprel and high calcium, atrial contractility is maintained via Isuprel’s c-AMP activation.
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