Abstract
3-iodothyronamine (T1AM) is an endogenous compound which shares structural and functional features with biogenic amines and is able to interact with a specific class of receptors, designed as trace amine associated receptors. T1AM has significant physiological effects in mammals and produces a reversible, dose-dependent negative inotropic and chronotropic effect in heart. The aim of the present study was to investigate if T1AM is able to reduce irreversible tissue injury in isolated rat hearts subjected to ischemia and reperfusion, as evaluated by triphenyltetrazolium chloride staining. We observed that T1AM reduced infarct size at concentrations (125 nM to 12.5 μM) which did not produce any significant hemodynamic action. The dose–response curve was bell-shaped and peaked at 1.25 μM. T1AM-induced cardioprotection was completely reversed by the administration of chelerythrine and glibenclamide, suggesting a protein kinase C and K +ATP -dependent pathway, while it was not additive to the protection induced by cyclosporine A, suggesting modulation of mitochondrial permeability transition. At cardioprotective concentration, T1AM reduced the time needed for cardiac attest during ischemia, but it did not affect sarcoplasmatic reticulum Ca2+ handling, as demonstrated by unaltered ryanodine receptor binding properties. In conclusion, in isolated rat heart T1AM produces a cardioprotective effect which is mediated by a protein kinase C and K +ATP -dependent pathway and is probably linked to modulation of mitochondrial permeability transition and/or ischemic arrest time.
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Frascarelli, S., Ghelardoni, S., Chiellini, G. et al. Cardioprotective Effect of 3-Iodothyronamine in Perfused Rat Heart Subjected to Ischemia and Reperfusion. Cardiovasc Drugs Ther 25, 307–313 (2011). https://doi.org/10.1007/s10557-011-6320-x
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DOI: https://doi.org/10.1007/s10557-011-6320-x