3-Iodothyroacetic acid (TA1) is an end product of thyroid hormone metabolism. So far, it is not known if TA1 is present in mouse brain and if it has any pharmacological effects. EXPERIMENTAL APPROACH TA1 levels in mouse brain were measured by HPLC coupled to mass spectrometry. After i.c.v. administration of exogenous TA1(0.4, 1.32 and 4 μg·kg−1) to mice, memory acquisition-retention (passive avoidance paradigm with a light-dark box), pain threshold to thermal stimulus (51.5°C; hot plate test) and plasma glucose (glucorefractometer) were evaluated. Similar assays were performed in mice pretreated with s.c. injections of the histamine H1 receptor antagonist pyrilamine (10 mg·kg−1) or the H2 receptor antagonist zolantidine (5 mg·kg−1). TA1 (1.32 and 4 μg·kg−1) was also given i.c.v. to mice lacking histidine decarboxylase (HDC−/−) and the corresponding WT strain. TA1 was found in the brain of CD1 but not of HDC mice. Exogenous TA1 induced amnesia (at 0.4 μg·kg−1), stimulation of learning (1.32 and 4 μg·kg−1), hyperalgesia (0.4, 1.32 and 4 μg·kg−1) and hyperglycaemia (1.32 and 4 μg·kg−1). All these effects were modulated by pyrilamine and zolantidine. In HDC−/− mice, TA1 (1.32 and 4 μg·kg−1) did not increase plasma glucose or induce hyperalgesia. Behavioural and metabolic effects of TA1 disclosed interactions between the thyroid and histaminergic systems.

Histamine mediates behavioural and metabolic effects of 3-iodothyroacetic acid, an endogenous end product of thyroid hormone metabolism / Claudia Musilli; Gaetano De Siena; Maria Elena Manni; Andrea Logli; Elisa Landucci; Riccardo Zucchi; Alessandro Saba;Riccardo Donzelli; Maria Beatrice Passani; Gustavo Provensi; Laura Raimondi. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - ELETTRONICO. - 171:(2014), pp. 3476-3484. [10.1111/bph.12697]

Histamine mediates behavioural and metabolic effects of 3-iodothyroacetic acid, an endogenous end product of thyroid hormone metabolism

MUSILLI, CLAUDIA;MANNI, MARIA ELENA;LANDUCCI, ELISA;PASSANI, MARIA BEATRICE;PROVENSI, GUSTAVO;RAIMONDI, LAURA
2014

Abstract

3-Iodothyroacetic acid (TA1) is an end product of thyroid hormone metabolism. So far, it is not known if TA1 is present in mouse brain and if it has any pharmacological effects. EXPERIMENTAL APPROACH TA1 levels in mouse brain were measured by HPLC coupled to mass spectrometry. After i.c.v. administration of exogenous TA1(0.4, 1.32 and 4 μg·kg−1) to mice, memory acquisition-retention (passive avoidance paradigm with a light-dark box), pain threshold to thermal stimulus (51.5°C; hot plate test) and plasma glucose (glucorefractometer) were evaluated. Similar assays were performed in mice pretreated with s.c. injections of the histamine H1 receptor antagonist pyrilamine (10 mg·kg−1) or the H2 receptor antagonist zolantidine (5 mg·kg−1). TA1 (1.32 and 4 μg·kg−1) was also given i.c.v. to mice lacking histidine decarboxylase (HDC−/−) and the corresponding WT strain. TA1 was found in the brain of CD1 but not of HDC mice. Exogenous TA1 induced amnesia (at 0.4 μg·kg−1), stimulation of learning (1.32 and 4 μg·kg−1), hyperalgesia (0.4, 1.32 and 4 μg·kg−1) and hyperglycaemia (1.32 and 4 μg·kg−1). All these effects were modulated by pyrilamine and zolantidine. In HDC−/− mice, TA1 (1.32 and 4 μg·kg−1) did not increase plasma glucose or induce hyperalgesia. Behavioural and metabolic effects of TA1 disclosed interactions between the thyroid and histaminergic systems.
2014
171
3476
3484
Goal 3: Good health and well-being for people
Claudia Musilli; Gaetano De Siena; Maria Elena Manni; Andrea Logli; Elisa Landucci; Riccardo Zucchi; Alessandro Saba;Riccardo Donzelli; Maria Beatrice Passani; Gustavo Provensi; Laura Raimondi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/876935
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