Objectives: 3-iodothyroacetic acid (TA1) is the major catabolite of 3-iodothyronamine in most tissues. The aim of the present work is to determine whether TA1 is physiologically present in rodent brain and whether administration of exogenous TA1 can produce significant functional effects. Methods: We measured TA1 concentration in mouse brain by HPLC coupled to mass spectrometry and we investigated whether administration of exogenous TA1 modified memory, pain perception and plasma glycemia. Fifteen min after intracerebroventricular (i.c.v.) injection of TA1 (0.4, 1.32 and 4 ugkg-1) memory acquisition-retention, pain threshold to a hot stimulus and plasma glycemia were evaluated on the light-dark box, on the hot plate (51.5°C) and by a glucorefractometer respectively. Parallel experiments were performed in mice pre-treated with subcutaneous injections of pyrilamine (10 mgkg-1) or zolantidine (5 mgkg-1), antagonists of histamine H1 and H2 receptors respectively. Furthermore, TA1 (1.32 and 4 ugkg-1) was i.c.v. injected in histidine decarboxylase null (HDC-/-) mice and in their HDC+/+ littermates. Results: TA1 was detected in CD1 mouse brain at concentrations on the order of 1 pmol/g of tissue. Pharmacological administration of TA1 included amnesia (at the dose of 0.4 ugkg-1), stimulation of learning (at 1.32 and 4 ugkg-1), hyperalgesia (at 0.4, 1.32 and 4 ugkg-1) and hyperglycemia (at 1.32 and 4 ugkg-1). These responses were inhibited by pyrilamine and zolantidine. In HDC-/- mice, TA1 (1.32 and 4 ugkg-1) failed to increase plasma glycemia and to reduce pain threshold. Conclusions: Exogenous TA1 produces significant behavioral and metabolic effects, possibly through activation of the histaminergic system. It remains to be determined whether similar effects can be produced physiologically by endogenous TA1.
Behavioral and metabolic effects of 3-iodothyroacetic acid: role of histamine
SABA, ALESSANDRO;CHIELLINI, GRAZIA;ZUCCHI, RICCARDO;
2014-01-01
Abstract
Objectives: 3-iodothyroacetic acid (TA1) is the major catabolite of 3-iodothyronamine in most tissues. The aim of the present work is to determine whether TA1 is physiologically present in rodent brain and whether administration of exogenous TA1 can produce significant functional effects. Methods: We measured TA1 concentration in mouse brain by HPLC coupled to mass spectrometry and we investigated whether administration of exogenous TA1 modified memory, pain perception and plasma glycemia. Fifteen min after intracerebroventricular (i.c.v.) injection of TA1 (0.4, 1.32 and 4 ugkg-1) memory acquisition-retention, pain threshold to a hot stimulus and plasma glycemia were evaluated on the light-dark box, on the hot plate (51.5°C) and by a glucorefractometer respectively. Parallel experiments were performed in mice pre-treated with subcutaneous injections of pyrilamine (10 mgkg-1) or zolantidine (5 mgkg-1), antagonists of histamine H1 and H2 receptors respectively. Furthermore, TA1 (1.32 and 4 ugkg-1) was i.c.v. injected in histidine decarboxylase null (HDC-/-) mice and in their HDC+/+ littermates. Results: TA1 was detected in CD1 mouse brain at concentrations on the order of 1 pmol/g of tissue. Pharmacological administration of TA1 included amnesia (at the dose of 0.4 ugkg-1), stimulation of learning (at 1.32 and 4 ugkg-1), hyperalgesia (at 0.4, 1.32 and 4 ugkg-1) and hyperglycemia (at 1.32 and 4 ugkg-1). These responses were inhibited by pyrilamine and zolantidine. In HDC-/- mice, TA1 (1.32 and 4 ugkg-1) failed to increase plasma glycemia and to reduce pain threshold. Conclusions: Exogenous TA1 produces significant behavioral and metabolic effects, possibly through activation of the histaminergic system. It remains to be determined whether similar effects can be produced physiologically by endogenous TA1.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
