Abstract
Glucagon can increase the force of contraction (FOC) in, for example, canine hearts. Currently, whether glucagon can also increase the FOC via cAMP-increasing receptors in the human atrium is controversial discussed. Glucagon alone did not (up to 1 µM) raise the FOC in human right atrial preparations (HAP). Only in the additional presence of the phosphodiesterase (PDE) 3 inhibitor cilostamide (1 µM) or 1 nM isoprenaline did glucagon raise the FOC, starting at 1 µM. The positive inotropic effects of glucagon in HAP were attenuated by a glucagon receptor antagonist (1 µM SC203972), but not by 100 nM exendin(9-39), a glucagon-like peptide-1 receptor (GLP-1R) antagonist. Glucagon (in the presence of cilostamide) demonstrated a reduced efficacy in elevating the FOC in HAP when compared with isoprenaline. In contrast to glucagon, exenatide alone, a GLP-1R agonist, starting at 1 nM, increased the FOC and was more potent and effective than glucagon in raising the FOC in HAP. The effects of exenatide on the FOC were attenuated by exendin(9-39). Hence, glucagon and GLP-1R agonists act functionally via different receptors in the human right atrium. Clinically, these data suggest that endogenous or exogenous glucagon can stimulate glucagon receptors in the human atrium, but only in the presence of PDE inhibitors.