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RESEARCH PRODUCT
Receptor identification and physiological characterisation of glucagon-like peptide-2 in the rat heart.
Tommaso AngeloneM.c. CerraE. FiliceDaniela PellegrinoSandra ImbrognoNicola AmodioA.m. QuintieriTeresa PasquaFlavia Mulèsubject
Maleendocrine systemmedicine.medical_specialtyCardiotonic AgentsNitric Oxide Synthase Type IIIMAP Kinase Signaling SystemG proteinEndocrinology Diabetes and MetabolismBlotting WesternMedicine (miscellaneous)Enzyme-Linked Immunosorbent AssayStimulationIn Vitro TechniquesBiologyReal-Time Polymerase Chain Reactionglucagon-like peptides-2 gut peptides cardiac performanceSettore BIO/09 - FisiologiaGlucagon-Like Peptide-1 Receptorchemistry.chemical_compoundInternal medicineCyclic AMPCyclic GMP-Dependent Protein KinasesGlucagon-Like Peptide 2Receptors GlucagonmedicineAnimalsCyclic adenosine monophosphatePhosphorylationRats WistarReceptorNutrition and Dieteticsdigestive oral and skin physiologyHeartPeptide FragmentsRatsPhospholambanEndocrinologyGene Expression RegulationchemistryInotropismGlucagon-Like Peptide-2 ReceptorCardiology and Cardiovascular MedicinecGMP-dependent protein kinasehormones hormone substitutes and hormone antagonistsIntestinal L CellsSignal Transductiondescription
Abstract Background and aims The anorexigenic glucagon-like peptide (GLP)-2 is produced by intestinal L cells and released in response to food intake. It affects intestinal function involving G-protein-coupled receptors. To verify whether GLP-2 acts as a cardiac modulator in mammals, we analysed, in the rat heart, the expression of GLP-2 receptors and the myocardial and coronary responses to GLP-2. Methods and results GLP-2 receptors were detected on ventricular extracts by quantitative real-time polymerase chain reaction (Q-RT-PCR) and Western blotting. Cardiac GLP-2 effects were analysed on Langendorff perfused hearts. Intracellular GLP-2 signalling was investigated on Langendorff perfused hearts and by Western blotting and enzyme-linked immunosorbent assay (ELISA) on ventricular extracts. By immunoblotting and Q-RT-PCR, we revealed the expression of ventricular GLP-2 receptors. Perfusion analyses showed that GLP-2 induces positive inotropism at low concentration (10–12 mol l −1 ), and negative inotropism and lusitropism from 10 to 10 mol l −1 . It dose-dependently constricts coronaries. The negative effects of GLP-2 were independent from GLP-1 receptors, being unaffected by exendin-3 (9–39) amide. GLP-2-dependent negative action involves Gi/o proteins, associates with a reduction of intracellular cyclic adenosine monophosphate (cAMP), an increase in extracellular signal regulated kinases 1 and 2 (ERK1/2) and a decrease in phospholamban phosphorylation, but is independent from endothelial nitric oxide synthase (eNOS) and protein kinase G (PKG). Finally, GLP-2 competitively antagonised β-adrenergic stimulation. Conclusions For the first time, to our knowledge, we found that: (1) the rat heart expresses functional GLP-2 receptors; (2) GLP-2 acts on both myocardium and coronaries, negatively modulating both basal and β-adrenergic stimulated cardiac performance; and (3) GLP-2 effects are mediated by G-proteins and involve ERK1/2.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-03-25 |