Receptor identification and physiological characterisation of glucagon-like peptide-2 in the rat heart.

Flavia Mule', Quintieri, Amodio, Filice, Pasqua, Angelone, Imbrogno, Pellegrino, Cerra

Risultato della ricerca: Article

26 Citazioni (Scopus)

Abstract

Background and aims: The anorexigenic glucagon-like peptide (GLP)-2 is producedby 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 myocardialand 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 investigatedon 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(0.001 nM), and negative inotropism and lusitropism from 0.1 nM. It dose-dependentlyconstricts coronaries. The negative effects of GLP-2 were independent from GLP-1receptors, being unaffected by exendin-3 (9-39) amide. GLP-2-dependent negative actioninvolves 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 b-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 b-adrenergic stimulated cardiac performance; and (3) GLP-2 effectsare mediated by G-proteins and involve ERK1/2.
Lingua originaleEnglish
pagine (da-a)486-494
Numero di pagine9
RivistaNMCD. NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
Volume22
Stato di pubblicazionePublished - 2012

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All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

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