Explore chapters and articles related to this topic
Peptidases and Peptides at the Blood-Brain Barrier
Published in Gerard O’Cuinn, Metabolism of Brain Peptides, 2020
Janet Brownlees, Carvell Williams
Vasopressin, a potent vasoconstrictor and modulator of blood-brain water transport (and substance P, a vasodilator peptide), bind to cerebral micro vessels via specific receptors. Their actions on vascular tone and on BBB permeability are mediated via activation of protein kinase C (PKC)72,95 suggesting that phosphorylation of specific substrate proteins may be involved. The effects of vasopressin on the affinity of leucine and phenylalanine for the large neutral amino acid transporter may be regulated by phosphorylation of the transporter.72 Arginine vasopressin (AVP) is reported to affect PKC after peripheral but not after central administration, suggesting that vasopressin receptors may be present only on the luminal membrane of the cerebral vasculature.72 AVP receptors at the BBB are of the VI type which mediate the contraction of smooth muscle. Binding of AVP to these receptors leads to a rapid increase in intracellular calcium in rat hippocampal endothelial cells.96 Vasopressin, like angiotensin II, is involved in the regulation of K+ transport across the BBB by inhibiting K+ channels via their action on G proteins.97
Metabolomics in normal and pathologic pregnancies
Published in Moshe Hod, Vincenzo Berghella, Mary E. D'Alton, Gian Carlo Di Renzo, Eduard Gratacós, Vassilios Fanos, New Technologies and Perinatal Medicine, 2019
Antonio Ragusa, Alessandro Svelato, Sara D'Avino
Increased plasma levels of phenylalanine and tyrosine have been observed in most analyses of amino acid biomarkers in obesity and type 2 diabetes (47). Changes in these amino acids could be explained by several factors. One hypothesis is that the increased circulating levels of the BCAAs compete with the aromatic amino acids for uptake into tissues through the shared large neutral amino acid transporter (LAT1) (49). Another possible explanation is that increasing liver dysfunction associated with metabolic unwellness results in decreased phenylalanine and tyrosine metabolism, leading to their elevated levels in plasma.
Gene Transfer into Human Hematopoietic Stem Cells
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Serguei Kisselev, Tatiana Seregina, Richard K. Burt, Charles J. Link
The use of pseudotyped vector systems based on the feline endogenous retrovirus envelope RD114 appears to be even more efficient than amphotropic or GALV envelopes. These vectors use the neutral amino acid transporter as a receptor.64 Kelly and colleagues reported efficient stable transduction of human NOD-SCID mouse repopulating cells (90%) using RD114 pseudotyped MoMuLV derived vector as demonstrated by enhanced green fluorescent protein (EGFP) reporter gene fluorescence.65
Gut-brain communication in COVID-19: molecular mechanisms, mediators, biomarkers, and therapeutics
Published in Expert Review of Clinical Immunology, 2022
Tameena Wais, Mehde Hasan, Vikrant Rai, Devendra K. Agrawal
The presence of ACE-2 in the GI tract has significant impact on the intestinal microbiota. A study in ACE-2 knockout mice revealed a decrease in the expression of antimicrobial agents which caused an alteration in the gut microbiome composition [64]. The role of ACE-2 in the small intestine is non-catalytic. ACE-2 in the lower GI stimulates the sodium-dependent neutral amino acid transporter B(0)AT1 (Figure 2b). This transporter is responsible for the transport of neutral amino acids for absorption [64]. B(0)AT1 plays a fundamental role in the absorption of amino acids including tryptophan, alanine, asparagine, and histidine [65]. Tryptophan plays a significant role in the kynurenine pathway, which is the process that converts tryptophan to nicotinamide [65]. Nicotinamide is involved in the mTOR pathway in the intestinal epithelium responsible for transcribing antimicrobial peptides [66]. With a decreased expression of antimicrobial peptides, the gut microbiota is altered.
Discovery of differentially expressed genes in the intestines of Pelteobagrus vachellii within a light/dark cycle
Published in Chronobiology International, 2020
Chuanjie Qin, Jiaxian Sun, Jun Wang, Yongwang Han, He Yang, Qingchao Shi, Yunyun Lv, Peng Hu
Moreover, a diurnal rhythmicity was noted for peptide absorption, for example, in nocturnal animals, the L-histidine absorption peak occurs during the dark phase(Furuya and Yugari 1974), which is coincident with higher expression levels of peptide transporter HPEPT1 (PEPT1) in the the dark compared with that in the light (Pan et al. 2002). In this study, b(0,+)-type amino acid transporter 1, sodium-coupled neutral amino acid transporter B, sodium-dependent neutral amino acid transporter 3, and excitatory amino acid transporter 1, all displayed upregulation at night, which contrasted with that of low affinity cationic amino acid transporter 2, a large neutral amino acids transporter. Excitatory amino acid transporter 1 is a sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate, L-aspartate, and D-aspartate (Arriza et al. 1994). The high-affinity transport of large neutral amino acids (e.g., phenylalanine, tyrosine, leucine, arginine, and tryptophan) is affected by sodium-independent, large neutral amino acids transporters. The peak time of mRNA expression was different for digestive enzymes and amino acid transporters within a light/dark cycle, which might suggest that the digestion and absorption of different amino acids was occurred at different times. Similarly, Senegalese sole (Solea senegalensis) showed their highest post-larval protein retention capacities when fed at nighttime (Marinho et al. 2014).
The role of pharmacogenomics in adverse drug reactions
Published in Expert Review of Clinical Pharmacology, 2019
Ramón Cacabelos, Natalia Cacabelos, Juan C. Carril
The pharmacogenomic machinery is integrated by a series of genes coding for enzymes and proteins which are determinant for drug targeting and processing, as well as critical components of the epigenetic machinery responsible for the regulation of gene expression [27]. The genes involved in the pharmacogenomic response to drugs fall into five major categories: (i) genes associated with disease pathogenesis; (ii) genes associated with the mechanism of action of drugs (enzymes, receptors, transmitters, messengers); (iii) genes associated with drug metabolism (phase I-II reaction enzymes)(Table 1); (iv) genes associated with drug transporters: (a) ATPase (P-type subfamily)(41 members), V-type (Vacuolar H+-ATPase subunit)(23 members), and ATPase (F-type subfamily)(16 members); (b) ATP-binding cassette transporters (Subfamily A)(ABC1)(12 members), Subfamily B (MDR/TAP)(10 members), Subfamily C (CFTR/MRP)(13 members), Subfamily D (ALD)(4 members), Subfamily E (OABP)(1 member), Subfamily F (GCN20)(3 members), and Subfamily G (WHITE)(5 members); and (c) Solute carriers (High-affinity glutamate and neutral amino acid transporter family (SLC1)(>300 members), (Table 2); and (v) pleiotropic genes involved in multifaceted cascades and metabolic reactions [4–6,25–27,37].