Imidazole-4-acetic acid, a new lead structure for interaction with the taurine transporter in outer blood-retinal barrier cells

Valembois, Sophie; Krall, Jacob; Frølund, Bente; Steffansen, Bente

doi:10.1016/j.ejps.2017.02.041

Cited by 7 publications

(13 citation statements)

References 45 publications

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“…In vertebrate retina, the taurine transporter (TAUT) is largely responsible for retinal transport of GABA, in contrast to the brain, where the GABA transporter has a larger functional role [ 84 ]. Retinal taurine influx is significantly inhibited in a concentration-dependent manner by both GABA and by I4AA [ 85 ]. GABA transporter 2 (GAT-2, also known as BGT-1) is also a taurine transporter [ 86 ], although its affinity for GABA is ~30× higher than its affinity for taurine [ 87 , 88 ].…”

Section: Resultsmentioning

confidence: 99%

Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined

Villar‐Briones

Aird

2018

Toxins

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Small metabolites and peptides in 17 snake venoms (Elapidae, Viperinae, and Crotalinae), were quantified using liquid chromatography-mass spectrometry. Each venom contains >900 metabolites and peptides. Many small organic compounds are present at levels that are probably significant in prey envenomation, given that their known pharmacologies are consistent with snake envenomation strategies. Metabolites included purine nucleosides and their bases, neurotransmitters, neuromodulators, guanidino compounds, carboxylic acids, amines, mono- and disaccharides, and amino acids. Peptides of 2–15 amino acids are also present in significant quantities, particularly in crotaline and viperine venoms. Some constituents are specific to individual taxa, while others are broadly distributed. Some of the latter appear to support high anabolic activity in the gland, rather than having toxic functions. Overall, the most abundant organic metabolite was citric acid, owing to its predominance in viperine and crotaline venoms, where it chelates divalent cations to prevent venom degradation by venom metalloproteases and damage to glandular tissue by phospholipases. However, in terms of their concentrations in individual venoms, adenosine, adenine, were most abundant, owing to their high titers in Dendroaspis polylepis venom, although hypoxanthine, guanosine, inosine, and guanine all numbered among the 50 most abundant organic constituents. A purine not previously reported in venoms, ethyl adenosine carboxylate, was discovered in D. polylepis venom, where it probably contributes to the profound hypotension caused by this venom. Acetylcholine was present in significant quantities only in this highly excitotoxic venom, while 4-guanidinobutyric acid and 5-guanidino-2-oxopentanoic acid were present in all venoms.

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Section: Resultsmentioning

confidence: 99%

Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined

Villar‐Briones

Aird

2018

Toxins

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“…A recently identified ligand of TauT, IAA (Valembois et al. ), inhibited the taurine uptake at neutral pH and slightly acidic pH at 52 nmol/L taurine, but not at 100 μ mol/L, pH 6.0 where PAT1 was dominating. It was an interesting finding that IAA may be a selective TauT inhibitor, since most substrates of TauT such as, for example, taurine, GABA, and β ‐Ala are also substrates of PAT1 (Frølund et al.…”

Section: Discussionmentioning

confidence: 98%

“…Therefore, the osmotic effect is less on filter-grown cells and in situations were more solute is transported into the cells, as under slightly acidic conditions were PAT1 transports taurine. A recently identified ligand of TauT, IAA (Valembois et al 2017), inhibited the taurine uptake at neutral pH and slightly acidic pH at 52 nmol/L taurine, but not at 100 lmol/L, pH 6.0 where PAT1 was dominating. It was an interesting finding that IAA may be a selective TauT inhibitor, since most substrates of TauT such as, for example, taurine, GABA, and b-Ala are also substrates of PAT1 (Frølund et al 2013).…”

Section: Taurine Absorption Was Facilitated By Pat1 In Vitromentioning

confidence: 92%

“…Taurine concentrations of 0.052, 0.1, 2, 5, 10, 25, and 50 mmol/L in MES buffer were investigated at pH 6.0. The uptake of 52 nmol/L taurine (1 lCi/mL [ 3 H]-taurine) at pH 7.4 was also measured in the presence of 20 mg/mL BCH, 20 mg/mL Sar, 10 mmol/L imidazole-4-acetic acid (IAA), which was recently identified as a ligand of TauT (Valembois et al 2017), and 20 mg/mL Pro. The taurine (0.1 mmol/L, 1 lCi/mL [ 3 H]-taurine) uptake at pH 6.0 was likewise measured in the presence of 20 mg/mL BCH, 20 mg/mL Sar or either 10 mmol/L of Sar, Pro, BCH, and IAA.…”

Section: Taurine Uptake In Caco-2 Cellsmentioning

confidence: 99%

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Oral and intravenous pharmacokinetics of taurine in sprague-dawley rats: the influence of dose and the possible involvement of the proton-coupled amino acid transporter, PAT1, in oral taurine absorption

et al. 2017

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Taurine is involved in various physiological processes, and one of the most abundant amino acids in human. The aim was to investigate the mechanism for intestinal absorption of taurine in vivo using also in vitro mechanistic studies. Taurine absorption was measured in male Sprague‐Dawley rats at 10–997 mg/kg and 1–30 mg/kg for oral and intravenous administration, respectively. Oral absorption was measured in the presence of substrates for the proton‐coupled amino acid transporter, PAT1, that is, 200 mg/kg proline (Pro) and sarcosine (Sar), and in the presence of 2‐Amino‐2‐norbornanecarboxylic acid (BCH) (200 mg/kg). BCH is not an inhibitor of PAT1 or the taurine transporter, TauT, hence it was included as a negative control. In vitro studies investigating the transport mechanism of taurine were conducted in human intestinal Caco‐2 cells. The pharmacokinetic investigations showed that intestinal taurine absorption was not saturable at the investigated doses, but that the time (t max) to reach the maximal plasma concentration (C max) increased with dose. Furthermore, Sar and Pro, but not BCH, decreased taurine C max. In vitro it was clearly shown that PAT1 mediated the cellular uptake of taurine and thereby facilitated the transepithelial taurine transport, which could be inhibited by Pro and Sar, but not BCH. In vivo and in vitro results suggest that taurine absorption from the intestine is caused by PAT1.

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“…[11][12][13][14] Histamine is further oxidized to imidazole-4-acetate, a γ-aminobutyric acid-type A receptor agonist, and type C receptor antagonist, whose administration to animals reduces motor activity, enhances seizures, and allodynia and leads to a sleep-like state with seizures. [15][16][17][18] Histamine can alternatively progress to N-acetylhistamine which acts as a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a regulator of body temperature, a vasodilator and a centrally acting neurotransmitter. 19 Excess of dietary histidine is irreversibly degraded to trans-urocanate by the rate-limiting action of histidine ammonia-lyase (HAL) or histidase, an enzyme highly expressed in the surface layer (stratum corneum) of the skin and in the liver.…”

Section: Introductionmentioning

confidence: 99%

Rapid and simultaneous determination of histidine metabolism intermediates in human and mouse microbiota and biomatrices

et al. 2021

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Histidine metabolism is a key pathway physiologically involved in satiety, recognition memory, skin, and neural protection and allergic diseases. Microbiologicallyproduced imidazole propionate induces type II diabetes and interferes with glucose lowering drugs. Despite their determinant health implications, no single method simultaneously assesses histidine metabolites in urine, feces, and microbiota. The aim of this study was to develop a simple, rapid, and sensitive method for the determination of histidine and its major bioactive metabolites histamine, N-acetylhistamine, imidazole-4-acetate, cis-urocanate, trans-urocanate, glutamate and imidazole propionate, using ultrahigh-performance liquid chromatography with electrospray ionization tandem mass spectrometry. An innovative simple extraction method from small aliquots of human and mice urine, feces and

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Imidazole-4-acetic acid, a new lead structure for interaction with the taurine transporter in outer blood-retinal barrier cells

Cited by 7 publications

References 45 publications

Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined

Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined

Oral and intravenous pharmacokinetics of taurine in sprague-dawley rats: the influence of dose and the possible involvement of the proton-coupled amino acid transporter, PAT1, in oral taurine absorption

Rapid and simultaneous determination of histidine metabolism intermediates in human and mouse microbiota and biomatrices

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