title: Characterization of 3-iodothyronamine in vitro dynamics by mathematical modeling.
abstract: 3-Iodothyronamine (T1AM) is regarded as a hormone-like substance thanks to its endogenous nature, its interaction with specific receptors trace amine-associated receptor 1 and its biological effects. We characterized T1AM transport and conversion in an in vitro culture of H9c2 murine cells, after a T1AM bolus injection. Samples of cell medium culture and cell lysate were assayed by high-performance liquid chromatography coupled to tandem mass spectrometry. We performed comparative experiments by adding to T1AM bolus amino oxidase inhibitors as iproniazid, pargyline (monoamine oxidase, MAO inhibitors), aminoguanidine, and semicarbazide (semicarbazide-sensitive amino oxidase, SSAO inhibitors). A mathematical model was developed, based on the assumption that T1AM is transported with a mechanism that is typical of hormone transport (i.e., EGF or insulin). We noticed that surface receptors downregulation could play a major role in T1AM dynamics. We also estimated that T1AM catabolism is mainly affected by MAO inhibitors, which produce a dramatic decrease in the kinetic constants related to T1AM degradation, while no significant changes were observed in experiments with SSAO inhibitors.
authors.affiliation: Research Center "E. Piaggio", Faculty of Engineering, University of Pisa, Via Diotisalvi 2, 56126, Pisa, PI, Italy, g.orsi@centropiaggio.unipi.it.
authors.forename: Gianni
authors.initials: G
authors.lastname: Orsi
authors.forename: Sandra
authors.initials: S
authors.lastname: Ghelardoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Saba
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zucchi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vozzi
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007490:Iproniazid / Q000494:pharmacology; D051379:Mice; D008962:Models, Theoretical; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects; D010293:Pargyline / Q000494:pharmacology; D012663:Semicarbazides / Q000494:pharmacology; D013970:Thyronines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*
chemical_list: C487948:3-iodothyronamine; D015815:Cell Adhesion Molecules; D006146:Guanidines; D007328:Insulin; D012663:Semicarbazides; D013970:Thyronines; C010059:carbamylhydrazine; D004815:Epidermal Growth Factor; D010293:Pargyline; D007490:Iproniazid; D006631:Amine Oxidase (Copper-Containing); C492678:semicarbazide-sensitive amine oxidase-vascular adhesion protein-1, mouse; D008995:Monoamine Oxidase; C004479:pimagedine