Cardioprotective effect of 3-iodothyronamine in perfused rat heart subjected to ischemia and reperfusion

Sabina Frascarelli, Sandra Ghelardoni, Grazia Chiellini, Elena Galli, Francesca Ronca, Thomas (Tom) Scanlan, Riccardo Zucchi

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

3-iodothyronamine (T 1AM) 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 1AM 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 1AM 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 1AM 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 1AM-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 1AM 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 1AM 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.

Original languageEnglish (US)
Pages (from-to)307-313
Number of pages7
JournalCardiovascular Drugs and Therapy
Volume25
Issue number4
DOIs
StatePublished - Aug 2011

Fingerprint

Reperfusion
Ischemia
Protein Kinase C
Permeability
Adenosine Triphosphate
Reticulum
Ryanodine Receptor Calcium Release Channel
Biogenic Amines
Glyburide
Cyclosporine
Amines
Mammals
Hemodynamics
Staining and Labeling
Wounds and Injuries
3-iodothyronamine
protein K
chelerythrine
triphenyltetrazolium

Keywords

  • 3-iodothyronamine
  • Heart
  • Ischemia
  • Reperfusion
  • Thyroid hormone

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Cardioprotective effect of 3-iodothyronamine in perfused rat heart subjected to ischemia and reperfusion. / Frascarelli, Sabina; Ghelardoni, Sandra; Chiellini, Grazia; Galli, Elena; Ronca, Francesca; Scanlan, Thomas (Tom); Zucchi, Riccardo.

In: Cardiovascular Drugs and Therapy, Vol. 25, No. 4, 08.2011, p. 307-313.

Research output: Contribution to journalArticle

Frascarelli, Sabina ; Ghelardoni, Sandra ; Chiellini, Grazia ; Galli, Elena ; Ronca, Francesca ; Scanlan, Thomas (Tom) ; Zucchi, Riccardo. / Cardioprotective effect of 3-iodothyronamine in perfused rat heart subjected to ischemia and reperfusion. In: Cardiovascular Drugs and Therapy. 2011 ; Vol. 25, No. 4. pp. 307-313.
@article{ccb31a4ac8e146779d0a8813aa73b40b,
title = "Cardioprotective effect of 3-iodothyronamine in perfused rat heart subjected to ischemia and reperfusion",
abstract = "3-iodothyronamine (T 1AM) 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 1AM 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 1AM 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 1AM 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 1AM-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 1AM 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 1AM 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.",
keywords = "3-iodothyronamine, Heart, Ischemia, Reperfusion, Thyroid hormone",
author = "Sabina Frascarelli and Sandra Ghelardoni and Grazia Chiellini and Elena Galli and Francesca Ronca and Scanlan, {Thomas (Tom)} and Riccardo Zucchi",
year = "2011",
month = "8",
doi = "10.1007/s10557-011-6320-x",
language = "English (US)",
volume = "25",
pages = "307--313",
journal = "Cardiovascular Drugs and Therapy",
issn = "0920-3206",
publisher = "Kluwer Academic Publishers",
number = "4",

}

TY - JOUR

T1 - Cardioprotective effect of 3-iodothyronamine in perfused rat heart subjected to ischemia and reperfusion

AU - Frascarelli, Sabina

AU - Ghelardoni, Sandra

AU - Chiellini, Grazia

AU - Galli, Elena

AU - Ronca, Francesca

AU - Scanlan, Thomas (Tom)

AU - Zucchi, Riccardo

PY - 2011/8

Y1 - 2011/8

N2 - 3-iodothyronamine (T 1AM) 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 1AM 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 1AM 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 1AM 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 1AM-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 1AM 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 1AM 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.

AB - 3-iodothyronamine (T 1AM) 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 1AM 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 1AM 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 1AM 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 1AM-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 1AM 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 1AM 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.

KW - 3-iodothyronamine

KW - Heart

KW - Ischemia

KW - Reperfusion

KW - Thyroid hormone

UR - http://www.scopus.com/inward/record.url?scp=80052297730&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052297730&partnerID=8YFLogxK

U2 - 10.1007/s10557-011-6320-x

DO - 10.1007/s10557-011-6320-x

M3 - Article

VL - 25

SP - 307

EP - 313

JO - Cardiovascular Drugs and Therapy

JF - Cardiovascular Drugs and Therapy

SN - 0920-3206

IS - 4

ER -