3-iodothyronamine(T1AM)anditsoxidativeproduct,3-iodotyhyroaceticacid(TTA1A),areknownto stimulate learningandinducehyperalgesiainmice.Weinvestigatedwhetheri)TA1maybegenerated in vivofromT1AM,ii)T1AMshareswithTA1theabilitytoactivatethehistaminergicsystem. TandemmassspectrometrywasusedtomeasureTA1andT1AMlevelsini)thebrainofmice following intracerebroventricular(i.c.v.)injectionofT1AM(11 μg kg1), withorwithoutpretreatment with clorgyline,(2.5mgkg1 i.p.), amonoamineoxidaseinhibitor;ii)themediumoforganotypic hippocampal slicesexposedtoT1AM(50nM).Inaddition,learningandpainthresholdwereevaluated by thelight–dark boxtaskandthehotplatetest,respectively,inmicepre-treatedsubcutaneouslywith pyrilamine(10mgkg1) orzolantidine(5mgkg1), 20minbeforei.c.v.injectionofT1AM(1.32and 11 μg kg1). T1AM-inducedhyperalgesia(1.32and11 μg kg1) wasalsoevaluatedinhistidine decarboxylase(HDC/) mice. T1AM andTA1brainlevelsincreasedinparallelinmiceinjectedwithT1AMwiththeTA1/T1AM averaging1.7%.Clorgylinepre-treatmentreducedtheincreaseinbothT1AMandTA1.TA1wasthemain T1AM metabolitedetectedinthehippocampalpreparations.Pretreatmentwithpyrilamineorzolanti- dine preventedthepro-learningeffectof1.32and4 μg kg1 T1AM whilehyperalgesiawasconservedat the doseof11 μg kg1 T1AM. T1AMfailedtoinducehyperalgesiainHDC/ mice atallthedoses. In conclusion,TA1generatedfromT1AM,butalsoT1AM,appearstoactbymodulatingthe histaminergic system.
In the brain of mice,3-iodothyronamine(T1AM) is converted into 3-iodothyroaceticacid(TA1) and it is included within the signaling network connecting thyroid hormone metabolites with histamine / Laurino, Annunziatina; DE Siena Gaetano ; Saba, Alessandro; Chiellini, Grazia; Landucci, Elisa; Zucchi, Riccardo; Raimondi, Laura. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - ELETTRONICO. - 761:(2015), pp. 130-134.
In the brain of mice,3-iodothyronamine(T1AM) is converted into 3-iodothyroaceticacid(TA1) and it is included within the signaling network connecting thyroid hormone metabolites with histamine
LAURINO, ANNUNZIATINA;DE SIENA, GAETANO;LANDUCCI, ELISA;RAIMONDI, LAURA
2015
Abstract
3-iodothyronamine(T1AM)anditsoxidativeproduct,3-iodotyhyroaceticacid(TTA1A),areknownto stimulate learningandinducehyperalgesiainmice.Weinvestigatedwhetheri)TA1maybegenerated in vivofromT1AM,ii)T1AMshareswithTA1theabilitytoactivatethehistaminergicsystem. TandemmassspectrometrywasusedtomeasureTA1andT1AMlevelsini)thebrainofmice following intracerebroventricular(i.c.v.)injectionofT1AM(11 μg kg1), withorwithoutpretreatment with clorgyline,(2.5mgkg1 i.p.), amonoamineoxidaseinhibitor;ii)themediumoforganotypic hippocampal slicesexposedtoT1AM(50nM).Inaddition,learningandpainthresholdwereevaluated by thelight–dark boxtaskandthehotplatetest,respectively,inmicepre-treatedsubcutaneouslywith pyrilamine(10mgkg1) orzolantidine(5mgkg1), 20minbeforei.c.v.injectionofT1AM(1.32and 11 μg kg1). T1AM-inducedhyperalgesia(1.32and11 μg kg1) wasalsoevaluatedinhistidine decarboxylase(HDC/) mice. T1AM andTA1brainlevelsincreasedinparallelinmiceinjectedwithT1AMwiththeTA1/T1AM averaging1.7%.Clorgylinepre-treatmentreducedtheincreaseinbothT1AMandTA1.TA1wasthemain T1AM metabolitedetectedinthehippocampalpreparations.Pretreatmentwithpyrilamineorzolanti- dine preventedthepro-learningeffectof1.32and4 μg kg1 T1AM whilehyperalgesiawasconservedat the doseof11 μg kg1 T1AM. T1AMfailedtoinducehyperalgesiainHDC/ mice atallthedoses. In conclusion,TA1generatedfromT1AM,butalsoT1AM,appearstoactbymodulatingthe histaminergic system.
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