3-Monoiodothyronamine: The rationale for its action as an endogenous adrenergic-blocking neuromodulator

Heinrich S. Gompf, Joel H. Greenberg, Gary Aston Jones, Alexandra G. Ianculescu, Tom S. Scanlan, Mary B. Dratman

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The investigations reported here were designed to gain insights into the role of 3-monoiodothyronamine (T1AM) in the brain, where the amine was originally identified and characterized. Extensive deiodinase studies indicated that T1AM was derived from the T4 metabolite, reverse triiodothyronine (revT3), while functional studies provided well-confirmed evidence that T1AM has strong adrenergic-blocking effects. Because a state of adrenergic overactivity prevails when triiodothyronine (T3) concentrations become excessive, the possibility that T3's metabolic partner, revT3, might give rise to an antagonist of those T3 actions was thought to be reasonable. All T1AM studies thus far have required use of pharmacological doses. Therefore we considered that choosing a physiological site of action was a priority and focused on the locus coeruleus (LC), the major noradrenergic control center in the brain. Site-directed injections of T1AM into the LC elicited a significant, dose-dependent neuronal firing rate change in a subset of adrenergic neurons with an EC50 = 2.7 μM, a dose well within the physiological range. Further evidence for its physiological actions came from autoradiographic images obtained following intravenous carrier-free 125I-labeled T1AM injection. These showed that the amine bound with high affinity to the LC and to other selected brain nuclei, each of which is both an LC target and a known T3 binding site. This new evidence points to a physiological role for T1AM as an endogenous adrenergic-blocking neuromodulator in the central noradrenergic system.

Original languageEnglish (US)
Pages (from-to)130-140
Number of pages11
JournalBrain research
Volume1351
DOIs
StatePublished - Sep 10 2010
Externally publishedYes

Fingerprint

Locus Coeruleus
Adrenergic Agents
Neurotransmitter Agents
Amines
Brain
Reverse Triiodothyronine
Adrenergic Neurons
Iodide Peroxidase
Injections
Triiodothyronine
Binding Sites
Pharmacology

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Gompf, Heinrich S. ; Greenberg, Joel H. ; Aston Jones, Gary ; Ianculescu, Alexandra G. ; Scanlan, Tom S. ; Dratman, Mary B. / 3-Monoiodothyronamine : The rationale for its action as an endogenous adrenergic-blocking neuromodulator. In: Brain research. 2010 ; Vol. 1351. pp. 130-140.
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3-Monoiodothyronamine : The rationale for its action as an endogenous adrenergic-blocking neuromodulator. / Gompf, Heinrich S.; Greenberg, Joel H.; Aston Jones, Gary; Ianculescu, Alexandra G.; Scanlan, Tom S.; Dratman, Mary B.

In: Brain research, Vol. 1351, 10.09.2010, p. 130-140.

Research output: Contribution to journalArticle

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