Glucagon increases contractility in ventricle but not in atrium of the rat heart.
This study evaluates the inotropic responses to glucagon in electrically driven isolated left and right atria as well as in right ventricular strips of rat heart. For comparison, the contractile effects resulting from stimulating beta-adrenoceptors with isoprenaline in atrial and ventricular tissues were also obtained. Glucagon (0.01-1 microM) produces a concentration-dependent positive inotropic effect in ventricular but not in atrial myocardium. Isoprenaline, however, increases contractility both in atrial and ventricular tissues. The nonselective phosphodiesterase (PDE) inhibitor 3-isobutylmethylxantine (IBMX, 10 microM) enhances the contractile effect of glucagon on ventricular myocardium. However, glucagon still failed to increase contractility in atrial myocardium in the presence of 10 microM, IBMX. Also, in left atria of rats pretreated with pertussis toxin, glucagon did not produce any positive inotropic effect, either alone or in the presence of 10 microM, IBMX. Western blotting analysis indicates that glucagon receptors expression is 5 times higher in ventricular than in atrial myocardium. Taken together, these results indicate that the lack of inotropic effect of glucagon in atrium is not due to Gi protein or PDEs activity but seems to be a consequence of a lower glucagon receptor density in this tissue.
Gonzalez-Muñoz
Carmen
C
Department of Pharmacology, Medical School, University of Murcia, Spain.
Nieto-Cerón
Susana
S
Cabezas-Herrera
Juan
J
Hernández-Cascales
Jesús
J
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005934:Glucagon / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D037342:Pertussis Toxin / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D005934:Glucagon; D037342:Pertussis Toxin; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine