Galanin/GalR1-3 system: A promising therapeutic target for myocardial ischemia/reperfusion injury - 09/12/18
pages | 7 |
Iconographies | 5 |
Vidéos | 0 |
Autres | 0 |
Graphical abstract |
Highlights |
• | Three new agonists of GalR1-3 receptors are synthesized on the basis of galanin fragment (2–15). |
• | They are able to reduce myocardial ischemia/reperfusion injury in rat models ex vivo and in vivo. |
• | The ligand [βAla14, His15]-galanin (2–15) shows the highest cardioprotective effectiveness. |
• | The galaninergic system represents a promising drug target for coronary heart disease. |
Abstract |
N-terminal fragments of galanin (2–11) and (2–15) are critical for binding to GalR1-3 receptors, members of the G-protein-coupled receptor superfamily, and are involved in myocardial protection against ischemia/reperfusion (I/R) injury. This study was designed to synthesize novel GalR1-3 agonists with improved properties and evaluate their efficiency as cardioprotective agents. Peptide agonists were synthesized by the automatic solid phase method using Fmoc technology and purified by preparative HPLC. Their chemical structure was identified by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Novel ligands of galanin receptors have greater solubility in water than natural galanin fragments. Cardiac function indices, myocardial infarct size and plasma activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) were measured to assess the peptide bioactivity. Infusion of optimal concentrations of the peptides (210–240 μM) after global ischemia enhanced functional recovery of isolated rat heart during reperfusion. Intravenous administration of the peptides in a dose range of 1–2 mg/kg at the onset of reperfusion significantly reduced infarct size and plasma levels of CK-MB and LDH in rats in vivo. The chimeric ligand [βAla14, His15]-galanin (2–15) exhibited the most beneficial effect on both models of I/R injury. The results suggest that pharmacological agonists of GalR1-3 receptors can be a rational basis for drug developments in the field of cardiovascular diseases.
Le texte complet de cet article est disponible en PDF.Keywords : Modified galanin fragments, Myocardial ischemia/reperfusion injury, Rat, Myocardial protection
Plan
Vol 109
P. 1556-1562 - janvier 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’achat d’article à l’unité est indisponible à l’heure actuelle.
Déjà abonné à cette revue ?