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3‐Iodothyroacetic acid lacks thermoregulatory and cardiovascular effects in vivo
Author(s) -
Hoefig Carolin S,
Jacobi Simon F,
Warner Amy,
Harder Lisbeth,
Schanze Nancy,
Vennström Björn,
Mittag Jens
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13131
Subject(s) - brown adipose tissue , heart rate , endocrinology , in vivo , hypothermia , medicine , kidney , thermogenesis , thermoregulation , bradycardia , blood pressure , adipose tissue , cardiovascular physiology , chemistry , pharmacology , biology , microbiology and biotechnology
Background and Purpose 3‐Iodothyronamine (3‐T 1 AM) is an endogenous thyroid hormone derivative reported to induce strong hypothermia and bradycardia within minutes upon injection in rodents. Although 3‐T 1 AM is rapidly converted to several other metabolites in vivo , these strong pharmacological responses were solely attributed to 3‐T 1 AM, leaving potential contributions of downstream products untested. We therefore examined the cardiometabolic effects of 3‐iodothyroacetic acid (TA 1 ), the main degradation product of 3‐T 1 AM. Experimental Approach We used a sensitive implantable radiotelemetry system in C57/Bl6J mice to study the effects of TA 1 on body temperature and heart rate, as well as other metabolic parameters. Key Results Interestingly, despite using pharmacological TA 1 doses, we observed no effects on heart rate or body temperature after a single TA 1 injection (50 mg·kg −1 , i.p.) compared to sham‐injected controls. Repeated administration of TA 1 (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 TA 1 compared to sham‐injected controls. Conclusions and Implications Our data therefore conclusively demonstrate that TA 1 does not contribute to the cardiovascular or thermoregulatory effects observed after 3‐T 1 AM administration in mice, suggesting that the oxidative deamination constitutes an important deactivation mechanism for 3‐T 1 AM with possible implications for cardiovascular and thermoregulatory functions.