title: Vasodilator Effect of Glucagon: Receptorial Crosstalk Among Glucagon, GLP-1, and Receptor for Glucagon and GLP-1.
abstract: Glucagon is known for its insulin-antagonist effect in the blood glucose homeostasis, while it also reduces vascular resistance. The mechanism of the vasoactive effect of glucagon has not been studied before; thereby we aimed to investigate the mediators involved in the vasodilatation induced by glucagon. The vasoactive effect of glucagon, insulin, and glucagon-like peptide-1 was studied on isolated rat thoracic aortic rings using a wire myograph. To investigate the mechanism of the vasodilatation caused by glucagon, we determined the role of the receptor for glucagon and the receptor for GLP-1, and studied also the effect of various inhibitors of gasotransmitters, inhibitors of reactive oxygen species formation, NADPH oxidase, prostaglandin synthesis, protein kinases, potassium channels, and an inhibitor of the Na(+)/Ca(2+)-exchanger. Glucagon causes dose-dependent relaxation in the rat thoracic aorta, which is as potent as that of insulin but greater than that of GLP-1 (7-36) amide. Vasodilatation by GLP-1 is partially mediated by the glucagon receptor. The vasodilatation due to glucagon evokes via the glucagon-receptor, but also via the receptor for GLP-1, and it is endothelium-independent. Contribution of gasotransmitters, prostaglandins, the NADPH oxidase enzyme, free radicals, potassium channels, and the Na(+)/Ca(2+)-exchanger is also significant. Glucagon causes dose-dependent relaxation of rat thoracic aorta in vitro, via the receptor for glucagon and the receptor for GLP-1, while the vasodilatation evoked by GLP-1 also evolves partially via the receptor for glucagon, thereby, a possible crosstalk between the 2 hormones and receptors could occur.
authors.affiliation: 2nd Department of Medicine and Nephrological Center University of Pécs, Pécs, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Sélley
authors.affiliation: 2nd Department of Medicine and Nephrological Center University of Pécs, Pécs, Hungary.
authors.forename: S
authors.initials: S
authors.lastname: Kun
authors.affiliation: Medical Clinic for Nephrology and Internal Intensive Care, Charité Campus Virchow Klinikum and Experimental and Clinical Research Center (ECRC), Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: I A
authors.initials: IA
authors.lastname: Szijártó
authors.affiliation: 2nd Department of Medicine and Nephrological Center University of Pécs, Pécs, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Kertész
authors.affiliation: 2nd Department of Medicine and Nephrological Center University of Pécs, Pécs, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Wittmann
authors.affiliation: 2nd Department of Medicine and Nephrological Center University of Pécs, Pécs, Hungary.
authors.forename: G A
authors.initials: GA
authors.lastname: Molnár
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D064426:Gasotransmitters / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk / Q000187:drug effects*; D018027:Receptors, Glucagon / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D064426:Gasotransmitters; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D007473:Ion Channels; D026901:Membrane Transport Proteins; D018027:Receptors, Glucagon; D014665:Vasodilator Agents; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D019255:NADPH Oxidases; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases