Tyrosine hydroxylase conditional knockout mice reveal peripheral tissue-dependent differences in dopamine biosynthetic pathways.
Fiche publication
Date publication
mars 2021
Journal
The Journal of biological chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr METZGER Daniel
Tous les auteurs :
Miyajima K, Kawamoto C, Hara S, Mori-Kojima M, Ohye T, Sumi-Ichinose C, Saito N, Sasaoka T, Metzger D, Ichinose H
Lien Pubmed
Résumé
Dopamine (DA) exerts well-known functions in the brain as a neurotransmitter. In addition, it plays important physiological roles in peripheral organs, but it is largely unknown how and where peripheral DA is synthesized and regulated. Catecholamines (CAs) in peripheral tissues are either produced within the tissue itself and/or derived from sympathetic neurons, which release neurotransmitters for uptake by peripheral tissues. To evaluate DA-producing ability of each peripheral tissue, we generated conditional KO mice (cKO mice) in which the tyrosine hydroxylase (TH) gene is ablated in the sympathoadrenal system, thus eliminating sympathetic neurons as a DA source. We then examined the alterations in the noradrenaline (NA), DA, and DOPA contents in peripheral organs and performed immunohistochemical analyses of TH-expressing cells. In the heart and pancreas of cKO mice, both the TH protein and NA levels were significantly decreased, and the DA contents were decreased in parallel with NA contents, indicating that the DA supply originated from sympathetic neurons. We found TH-immunoreactive cells in the stomach and lung, where the TH protein showed a decreasing trend but the DA levels were not decreased in cKO mice. Moreover, we found a significant correlation between the DA content in the kidney and the plasma DOPA concentration, suggesting that the kidney takes up DOPA from blood to make DA. The above data unravel differences in the DA biosynthetic pathway among tissues and support the role of sympathetic neurons as a DA supplier.
Mots clés
3,4-dihydroxyphenylalanine (dopa), adrenal, dopamine, gene knockout, heart, noradrenaline, pancreas, stomach, sympathoadrenal system, tyrosine hydroxylase
Référence
J Biol Chem. 2021 Mar 15;:100544