title: Cardioprotective effect of 3-iodothyronamine in perfused rat heart subjected to ischemia and reperfusion.
abstract: 3-iodothyronamine (T(1)AM) 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. T(1)AM 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 T(1)AM 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 T(1)AM 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. T(1)AM-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, T(1)AM reduced the time needed for cardiac attest during ischemia, but it did not affect sarcoplasmatic reticulum Ca(2+) handling, as demonstrated by unaltered ryanodine receptor binding properties. In conclusion, in isolated rat heart T(1)AM 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.
authors.affiliation: Dipartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Frascarelli
authors.forename: Sandra
authors.initials: S
authors.lastname: Ghelardoni
authors.forename: Grazia
authors.initials: G
authors.lastname: Chiellini
authors.forename: Elena
authors.initials: E
authors.lastname: Galli
authors.forename: Francesca
authors.initials: F
authors.lastname: Ronca
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Scanlan
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zucchi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010477:Perfusion; D015221:Potassium Channels / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013970:Thyronines / Q000494:pharmacology*
chemical_list: C487948:3-iodothyronamine; D002316:Cardiotonic Agents; D015221:Potassium Channels; D013970:Thyronines; C117780:mitochondrial K(ATP) channel; D011493:Protein Kinase C; D002118:Calcium