Thyronamine, a new inotropic agent: its cardiovascular effects and mechanism of action

Côté, Pierre; Polumbo, Ralph A.; Harrison, Donald C.

doi:10.1093/cvr/8.6.721

Cited by 15 publications

(7 citation statements)

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“…The response was remarkably reduced or abolished by adrenergic blockade, and it was concluded that T 0 AM induced adrenergic stimulation. Interestingly, after catecholamine depletion and/or adrenergic blockade, T 0 AM infusion produced an immediate negative inotropic effect [22], which is consistent with the results recently obtained in the isolated heart.…”

Section: H]-p-tyramine and [ 125 I]-t 1 Am But [ 125 I]-t 1 Am Was Nsupporting

confidence: 91%

“…While T 1 AM has been discovered only recently, over 30 years ago it was reported that in the anesthetized dog T 0 AM administration (8-16 mg/kg) increased the heart rate and inotropic indices such as dP/dt [22]. The response was remarkably reduced or abolished by adrenergic blockade, and it was concluded that T 0 AM induced adrenergic stimulation.…”

Section: H]-p-tyramine and [ 125 I]-t 1 Am But [ 125 I]-t 1 Am Was Nmentioning

confidence: 99%

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Cardiac effects of thyronamines

Zucchi

Ghelardoni²,

Chiellini³

2008

Heart Fail Rev

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3-Iodothyronamine (T(1)AM) is an endogenous compound derived from thyroid hormone through decarboxylation and deiodination, which interacts with a novel G protein-coupled receptor, known as trace amine-associated receptor 1 (TAAR1). TAAR1 and other receptors of this family are expressed in several tissues, including the heart. Functional effects have been observed after administration of exogenous T(1)AM: in the isolated heart, a negative inotropic and chronotropic action was produced, and the resistance to ischemic injury was increased, possibly as a consequence of an action on intracellular calcium homeostasis. Extracardiac effects include reduction of body temperature, increased lipid versus carbohydrate metabolism, and modulation of insulin secretion. T(1)AM might play an important physiological or pathophysiological role, and this signaling system might allow the development of new therapeutical agents.

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Section: H]-p-tyramine and [ 125 I]-t 1 Am But [ 125 I]-t 1 Am Was Nsupporting

confidence: 91%

Section: H]-p-tyramine and [ 125 I]-t 1 Am But [ 125 I]-t 1 Am Was Nmentioning

confidence: 99%

Cardiac effects of thyronamines

Zucchi

Ghelardoni²,

Chiellini³

2008

Heart Fail Rev

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show abstract

“…Although T 1 AM is a novel compound only recently discovered, a few studies with T 0 AM were performed over 30 yr ago. In the dog, intravenously administration of T 0 AM was seen to produce an increase in cardiac output and dP/dt, after a lag of ˜10 min (37). This effect was remarkably blunted by adrenergic blockade, suggesting that T 0 AM was acting by stimulating cate‐cholamine release.…”

Section: Discussionmentioning

confidence: 99%

Cardiac effects of 3‐iodothyronamine: a new aminergic system modulating cardiac function

et al. 2007

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3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

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“…Although T 1 AM is a novel compound only recently discovered, a few studies with other thyronamine congeners were performed many years ago. In the anaesthetized dog, thyronamine administration produced an increase in heart rate and cardiac inotropic state (Buu‐Hoi et al ., 1966; Buu‐Hoi et al ., 1969; Boissier et al ., 1973; Cote et al ., 1974). These effects appeared after a lag of about 10 min, and were remarkably blunted or abolished by adrenergic blockade, suggesting at the time that thyronamine induced catecholamine release.…”

Section: Endogenous Taar Ligands: (B) Thyronaminesmentioning

confidence: 99%

Trace amine‐associated receptors and their ligands

Zucchi

Chiellini

et al. 2006

British J Pharmacology

267

229

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Classical biogenic amines (adrenaline, noradrenaline, dopamine, serotonin and histamine) interact with specific families of G protein-coupled receptors (GPCRs). The term 'trace amines' is used when referring to p-tyramine, b-phenylethylamine, tryptamine and octopamine, compounds that are present in mammalian tissues at very low (nanomolar) concentrations. The pharmacological effects of trace amines are usually attributed to their interference with the aminergic pathways, but in 2001 a new gene was identified, that codes for a GPCR responding to p-tyramine and b-phenylethylamine but not to classical biogenic amines. Several closely related genes were subsequently identified and designated as the trace amineassociated receptors (TAARs). Pharmacological investigations in vitro show that many TAAR subtypes may not respond to p-tyramine, b-phenylethylamine, tryptamine or octopamine, suggesting the existence of additional endogenous ligands. A novel endogenous thyroid hormone derivative, 3-iodothyronamine, has been found to interact with TAAR1 and possibly other TAAR subtypes. In vivo, micromolar concentrations of 3-iodothyronamine determine functional effects which are opposite to those produced on a longer time scale by thyroid hormones, including reduction in body temperature and decrease in cardiac contractility. Expression of all TAAR subtypes except TAAR1 has been reported in mouse olfactory epithelium, and several volatile amines were shown to interact with specific TAAR subtypes. In addition, there is evidence that TAAR1 is targeted by amphetamines and other psychotropic agents, while genetic linkage studies show a significant association between the TAAR gene family locus and susceptibility to schizophrenia or bipolar affective disorder.

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Thyronamine, a new inotropic agent: its cardiovascular effects and mechanism of action

Cited by 15 publications

References 0 publications

Cardiac effects of thyronamines

Cardiac effects of thyronamines

Cardiac effects of 3‐iodothyronamine: a new aminergic system modulating cardiac function

Trace amine‐associated receptors and their ligands

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