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

Abstract

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.

Glucagon and Its Receptors in the Mammalian Heart

“…Cat [3,5,25] PCE [25] PIE [5,25,26] In vivo: PIE [5,27] PIE: papillary muscle [27] PIE: perfused heart [28] No PIE in heart failure [25,29] PIE in heart failure Dog [3,4] PIE [3,4,[30][31][32][33][34][35][36][37][38][39][40]] PCE [31,36] PIE [3,4,34,35,39,40] PIE [4] failing dog ventricle [40] Coronary perfusion enhanced Embryon-ic chick heart [41] PCE Frog [42] PIE Guinea pig [3,[43][44][45][46][47][48][49][50][51][52]…”