title: Glucagon Increases Beating Rate but Not Contractility in Rat Right Atrium. Comparison with Isoproterenol.
abstract: This study evaluated the chronotropic and inotropic responses to glucagon in spontaneously beating isolated right atria of rat heart. For comparison, we also investigated the effects resulting from stimulating β-adrenoceptors with isoproterenol in this tissue. Isoproterenol increased both atrial frequency and contractility but glucagon only enhanced atrial rate. The transcript levels of glucagon receptors were about three times higher in sinoatrial node than in the atrial myocardium. Chronotropic responses to glucagon and isoproterenol were blunted by the funny current (If) inhibitor ZD 7288. Inhibitors of protein kinase A, H-89 and KT-5720 reduced the chronotropic response to glucagon but not to isoproterenol. Inhibition of ryanodine receptors and calcium/calmodulin dependent protein kinase II (important regulators of sarcoplasmic reticulum Ca2+ release), with ruthenium red and KN-62 respectively, failed to alter chronotropic responses of either glucagon or isoproterenol. Non selective inhibition of phosphodiesterase (PDE) with 3-isobutylmethylxantine or selective inhibition of PDE3 or PDE4 with cilostamide or rolipram respectively did not affect chronotropic effects of glucagon or isoproterenol. Our results indicate that glucagon increases beating rate but not contractility in rat right atria which could be a consequence of lower levels of glucagon receptors in atrial myocardium than in sinoatrial node. Chronotropic responses to glucagon or isoproterenol are mediated by If current but not by sarcoplasmic reticulum Ca2+ release, neither are regulated by PDE activity.
authors.affiliation: Instituto de Bioingeniería, Universidad Miguel Hernández, Elche, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Elche, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Merino
authors.affiliation: Instituto de Bioingeniería, Universidad Miguel Hernández, Elche, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Elche, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Quesada
authors.affiliation: Departamento Farmacología; Facultad de Medicina; Universidad Murcia, Murcia, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Hernández-Cascales
mesh_terms: D000818:Animals; D016280:Atrial Function, Right / Q000187:drug effects* / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005934:Glucagon / Q000494:pharmacology*; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium; D058987:Phosphodiesterase 3 Inhibitors / Q000494:pharmacology; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D002227:Carbazoles; D007546:Isoquinolines; D058987:Phosphodiesterase 3 Inhibitors; D058988:Phosphodiesterase 4 Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C082246:ICI D2788; C057416:KT 5720; D005934:Glucagon; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide