Thyronamines are naturally occurring metabolites
of thyroid hormone that inhibit neural and cardiac function in animals
(November 2004)
The background of the study. Most actions of thyroid
hormone, in the form of triiodothyronine (T3), are mediated by changes
in gene activity, and the changes take hours or days. Some actions
of thyroid hormone are rapid, and presumably non-gene-based. Thyronamines,
which are decarboxylated and deiodinated derivatives of T3 may mediate
these latter actions. This study evaluated the actions of iodothyronamines
and their detection in animal tissues.
How the study was done and the results of the study.
Thyronamine (T0-amine) and several iodothyronamines stimulated cyclic
AMP production by kidney cells with type 1 trace amine receptors
(TAR1), a member of a family of receptors that are activated by
biogenic amines. The stimulation was dose-dependent, and there was
no stimulation of cells with dopamine or adrenergic receptors. T0-amine
and T1-amine did not activate T3 nuclear receptors, and T3 and thyroxine
(T4) did not activate TAR1 receptors.
T0-amine and T1-amine were isolated from extracts of mouse brain,
heart, liver, and blood. Administration of these two substances
to mice resulted in hypothermia (temperature fall from 37°C
to 29.5°C in 2 hours), inactivity, and a hunched-back posture
lasting 6 to 8 hours. T0-amine and T1-amine slowed the heart rate
in mice in 10 minutes, and this effect also lasted for 6 to 8 hours.
Conclusion T0-amine and T1-amine are naturally
occurring derivatives of T4 and T3 that act rapidly to inhibit neural
and cardiac activity.
The original article. Scanlan TS, Suchland KL,
Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley
DA, Bunzow JR, Ronca-Testoni S, Lin ET, Hatton D, Zucchi R, Grandy
DK. 3-Iodothyronamine is an endogenous and rapid-acting derivative
of thyroid hormone. Nat Med 2004;10:638-42.
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