rt of tryptophan, phenylalanine and tyrosine, both localized at the apical membrane of enterocytes. The

rt of tryptophan, phenylalanine and tyrosine, both localized at the apical membrane of enterocytes. The identical pattern of expression was observed for SLC3A1 and SLC7A9, that are involved in the influx transport of L-DOPA. In contrast, the enzymes DDC, SULT1A1/2/3, MAOA, MAOB and CYP2D6 harbored a cytoplasmic staining pattern. Furthermore expected, the L-DOPA efflux transporters SLC3A2 and SLC7A8 had been detected in the basolateral membrane of enterocytes. A low and diffuse staining pattern was observed for SLC16A10. Ultimately, no TH staining might be detected (Figure S1), in accordance with genomics analyses. According to these mined information, a scheme summarizing the predicted dopamine/trace amines metabolic pathways taking location in human enterocytes is shown in Figure 2.Int. J. Mol. Sci. 2021, 22,metabolism of dopamine and/or trace amines. This observation suggests that regionalization as an alternative to cell specificity could dictate the expression of such genes. At the protein level, a survey from the immunohistochemical analyses gathered in the Human Protein Atlas confirmed that enterocytes from the little intestine robustly express ACE2, SLC6A19 along with the 12 other proteins we identified as molecules of interest as a consequence of their involvement in the five of 16 metabolism of dopamine and/or trace amines (Figure 1). Extra facts regarding antibodies and tissues are presented in Section 4.Figure 1. Expression by human enterocytes of important molecules involved in dopamine/trace amines metabolic pathways: A by human enterocytes of key molecules involved in dopamine/trace amines metabolic pathways: survey on the Human Protein Atlas (proteinatlas.org/ (accessed on 24 24 September 2021)) permitted extractA survey with the Human Protein Atlas (proteinatlas.org/ (accessed on September 2021)) allowed extracting ing immunohistochemical data obtained on human small intestine for the following candidate molecules: angiotensinconverting enzyme two (ACE2), solute carrier family 6 HSV list member 19 (SLC6A19), solute carrier family members 3 member 1 (SLC3A1), solute carrier family 7 member 9 (SLC7A9), dopa-decarboxylase (DDC), sulfotransferase family members 1A member 1 (SULT1A1), sulfotransferase household 1A member two (SULT1A2), sulfotransferase family members 1A member 3 (SULT1A3), cytochrome P450 loved ones 2 subfamily D member six (CYP2D6), monoamine oxidase A (MAOA), monoamine oxidase B (MAOB), solute carrier family three member 2 (SLC3A2), solute carrier loved ones 7 member 8 (SLC7A8) and solute carrier family 6 member 10 (SLC16A10). Scale bar: 25 .2.two. Assessment of Co-Expression Links among ACE2 and Crucial Genes on the Dopamine/Trace Amines Metabolic Pathways in SARS-CoV2-Infected Human Intestinal Organoids We then sought to ascertain whether, in SARS-CoV2-infected human enterocytes, ACE2 co-regulates with DDC and/or important genes involved within the dopamine/trace amines metabolic pathways. To this aim, we re-assessed a lately published RNA-seq dataset obtained in the analysis of control vs. SARS-CoV2-infected human intestinal organoids [34]. In these experiments, the expression of ACE2 exhibited a HSP105 site peculiar kinetics characterized, at 24 h post-infection, by a dramatic drop of mRNA levels (by a element ten in two independent experiments; Figure S2), followed by a return to baseline levels at 60 h post-infection (Figure S2). Among the genes of interest that we focused on, a comparable silencing impact of SARS-CoV2 was observed at 24 h post-infection for SLC6A19 (the gene encoding the neutral amino acid transporter that physically interacts with