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Br J Pharmacol. 2015 Jul;172(13):3426-33. doi: 10.1111/bph.13131. Epub 2015 Jun 9.

3-Iodothyroacetic acid lacks thermoregulatory and cardiovascular effects in vivo.

Author information

1
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
2
Center of Brain Behavior and Metabolism CBBM/Medizinische Klinik I, University of Lübeck, Lübeck, Germany.

Abstract

BACKGROUND AND PURPOSE:

3-Iodothyronamine (3-T1 AM) is an endogenous thyroid hormone derivative reported to induce strong hypothermia and bradycardia within minutes upon injection in rodents. Although 3-T1 AM is rapidly converted to several other metabolites in vivo, these strong pharmacological responses were solely attributed to 3-T1 AM, leaving potential contributions of downstream products untested. We therefore examined the cardiometabolic effects of 3-iodothyroacetic acid (TA1 ), the main degradation product of 3-T1 AM.

EXPERIMENTAL APPROACH:

We used a sensitive implantable radiotelemetry system in C57/Bl6J mice to study the effects of TA1 on body temperature and heart rate, as well as other metabolic parameters.

KEY RESULTS:

Interestingly, despite using pharmacological TA1 doses, we observed no effects on heart rate or body temperature after a single TA1 injection (50 mg·kg(-1) , i.p.) compared to sham-injected controls. Repeated administration of TA1 (5 mg·kg(-1) , i.p. for 7 days) likewise did not alter body weight, food and water intake, heart rate, blood pressure, brown adipose tissue (BAT) thermogenesis or body temperature. Moreover, mRNA expression of tissue specific genes in heart, kidney, liver, BAT and lung was also not altered by TA1 compared to sham-injected controls.

CONCLUSIONS AND IMPLICATIONS:

Our data therefore conclusively demonstrate that TA1 does not contribute to the cardiovascular or thermoregulatory effects observed after 3-T1 AM administration in mice, suggesting that the oxidative deamination constitutes an important deactivation mechanism for 3-T1 AM with possible implications for cardiovascular and thermoregulatory functions.

PMID:
25765843
PMCID:
PMC4500376
DOI:
10.1111/bph.13131
[Indexed for MEDLINE]
Free PMC Article

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