Fundam Clin Pharmacol. 2023 May 30. doi: 10.1111/fcp.12925. Online ahead of print.
ABSTRACT
The aim of this work was to elucidate the role of GalR2 receptor activation in protecting the rat heart in vivo from I/R damage by a pharmacological peptide agonist WTLNSAGYLLGPβAH-OH (G1) and full-length rat galanin GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2 (G2) using M871, a selective inhibitor of GalR2. The peptides were prepared by the automatic solid phase synthesis using the Fmoc-strategy and purified by HPLC. 40-minute LAD coronary artery occlusion followed by a 60-minute reperfusion was performed. The criteria for damage/protection of the heart were the infarct size (IS) and plasma activity of CK-MB at the end of reperfusion. Intravenous injection of G1 or G2 at an optimal dose of 1 mg/kg at the 5th minute of reperfusion significantly reduced the IS (by 35 and 32%, respectively) and activity of CK-MB at the end of reperfusion (by 43 and 38%, respectively) compared with the control. Administration of M871 (8 mg/kg) 5 min before the onset of reperfusion abolished the effects of G1 on IS and CK-MB activity, returning them to control values. Co-administration of M871 (8 mg/kg) with G2 attenuated protective effect of G2 on both IS and plasma СK-MB activity. However, differences in these parameters between the M871+G2 and G2 groups did not reach statistical significance (P=0.139 and P=0.121, respectively). Thus, GalR2 is the principal receptor subtype that transduces the protective effects of galanin and ligand G1 in myocardial I/R injury. This suggests that GalR2-specific peptide agonists could be used as drug candidates for treating ischemic heart disease.
PMID:37249014 | DOI:10.1111/fcp.12925
