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sarcosine |
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CHEBI:15611 |
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A N-alkylglycine that is the N-methyl derivative of glycine. It is an intermediate in the metabolic pathway of glycine. |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:45442, CHEBI:45531, CHEBI:45614, CHEBI:45381, CHEBI:10876, CHEBI:12609, CHEBI:9029, CHEBI:15065, CHEBI:21765
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ChemicalBook:CB9712144, eMolecules:480611, ZINC000004658561 |
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Molfile
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SDF
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more structures >>
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Sarcosine, also known as N-methylglycine, or monomethylglycine, is a amino acid with the formula CH3N(H)CH2CO2H. It exists at neutral pH as the zwitterion CH3N+(H)2CH2CO2−, which can be obtained as a white, water-soluble powder. Like some amino acids, sarcosine converts to a cation at low pH and an anion at high pH, with the respective formulas CH3N+(H)2CH2CO2H and CH3N(H)CH2CO2−. Sarcosine is a close relative of glycine, with a secondary amine in place of the primary amine.
Sarcosine is ubiquitous in biological materials. It is used in manufacturing biodegradable surfactants and toothpastes as well as in other applications. It is also a reagent in organic synthesis.
Sarcosine is sweet to the taste. |
Read full article at Wikipedia
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InChI=1S/C3H7NO2/c1-4-2-3(5)6/h4H,2H2,1H3,(H,5,6) |
FSYKKLYZXJSNPZ-UHFFFAOYSA-N |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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See:
DOI
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Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
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Escherichia coli metabolite
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
glycine transporter 1 inhibitor
Any glycine transporter inhibitor that interferes with the action of glycine 1 transporters.
glycine receptor agonist
An agonist that binds to and activates glycine receptors
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
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View more via ChEBI Ontology
(methylamino)acetic acid
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ChemIDplus
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(methylamino)ethanoic acid
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NIST Chemistry WebBook
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L-sarcosine
Note: (2015-03-26) A misnomer which has been frequently used in the primary literature - sarcosine does not have a chiral centre, so cannot be either D or L. |
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ChEBI
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MeGly
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ChEBI
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methylaminoacetic acid
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NIST Chemistry WebBook
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N-methylaminoacetic acid
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NIST Chemistry WebBook
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N-Methylglycine
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KEGG COMPOUND
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Sar
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IUPAC
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Sarcosine
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KEGG COMPOUND
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SARCOSINE
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PDBeChem
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sarcosinic acid
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ChemIDplus
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107-97-1
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CAS Registry Number
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NIST Chemistry WebBook
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107-97-1
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CAS Registry Number
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ChemIDplus
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1699442
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Reaxys Registry Number
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Reaxys
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2018
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Gmelin Registry Number
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Gmelin
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Yang SY, Hong CJ, Huang YH, Tsai SJ (2010) The effects of glycine transporter I inhibitor, N-methylglycine (sarcosine), on ketamine-induced alterations in sensorimotor gating and regional brain c-Fos expression in rats. Neuroscience letters 469, 127-130 [PubMed:19944746] [show Abstract] Reduced N-methyl-D-aspartate receptor (NMDAR) function may contribute to the pathogenesis of schizophrenia. Sarcosine, a potent glycine transporter inhibitor, can increase synaptic glycine and then promote NMDAR function. We assessed the antipsychotic potential of sarcosine by comparing the abilities of sarcosine and clozapine to restore the prepulse inhibition (PPI) deficit, hyperlocomotion and regional brain c-Fos expression changes caused by an NMDAR antagonist, ketamine. Four groups of rats were given acute injections, including saline+saline, saline+30 mg/kg ketamine, 100mg/kg sarcosine+30 mg/kg ketamine, and 15 mg/kg clozapine+30 mg/kg ketamine. Both sarcosine and clozapine reversed the ketamine-induced PPI deficit and hyperlocomotion. They both did not change ketamine-induced increase in c-Fos expression in the prefrontal cortex and nucleus accumbens. However, in the olfactory bulb, sarcosine, but not clozapine, significantly reduced the ketamine-induced increase in c-Fos expression. Our animal study demonstrated that sarcosine may have antipsychotic potential. | Zhang HX, Lyons-Warren A, Thio LL (2009) The glycine transport inhibitor sarcosine is an inhibitory glycine receptor agonist. Neuropharmacology 57, 551-555 [PubMed:19619564] [show Abstract] Sarcosine is an endogenous amino acid that is a competitive inhibitor of the type I glycine transporter (GlyT1), an N-methyl-d-aspartate receptor (NMDAR) co-agonist, and an important intermediate in one-carbon metabolism. Its therapeutic potential for schizophrenia further underscores its clinical importance. The structural similarity between sarcosine and glycine and sarcosine's ability to serve as an NMDAR co-agonist led us to examine whether sarcosine is also an agonist at the inhibitory glycine receptor (GlyR). We examined this possibility using whole-cell recordings from cultured embryonic mouse hippocampal neurons and found that sarcosine evoked a dose-dependent, strychnine sensitive, Cl(-) current that cross-inhibited glycine currents. Sarcosine evoked this current with Li(+) in the extracellular solution to block GlyT1, in neurons treated with the essentially irreversible GlyT1 inhibitor N[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS), and in neurons plated in the absence of glia. These results indicate that the sarcosine currents did not result from GlyT1 inhibition or heteroexchange. We conclude that sarcosine is a GlyR agonist. | Centeno MV, Mutso A, Millecamps M, Apkarian AV (2009) Prefrontal cortex and spinal cord mediated anti-neuropathy and analgesia induced by sarcosine, a glycine-T1 transporter inhibitor. Pain 145, 176-183 [PubMed:19577367] [show Abstract] Sarcosine is a competitive inhibitor of glycine type 1 transporter. We hypothesized that it may have analgesic and anti-neuropathic efficacy by a dual action: affecting neurotransmission in the prefrontal cortex as well as within the spinal cord. In rats with spared nerve injury (SNI) oral sarcosine reduced mechanical sensitivity for the injured limb (anti-neuropathy or anti-allodynia) as well as for the uninjured limb (analgesia), showing better dose efficacy for the injured limb. Intrathecal administration of sarcosine was more effective in reducing mechanical sensitivity for the uninjured paw. In contrast, prefrontal cortex infusions of sarcosine acutely reduced mechanical sensitivity for the injured paw. Repeated daily oral sarcosine induced anti-neuropathy, observed only after days of repeated treatment; this long-term effect disappeared a few days after treatment cessation. The findings indicate that manipulating glycine-T1 transporter at multiple central sites can induce acute analgesia, as well as acute and long-term reduction in neuropathic pain behavior. Analgesic effects seem primarily mediated through spinal cord circuitry while anti-neuropathic effects seem mediated through prefrontal cortex circuitry, most likely through distinct molecular pathways. The results suggest that such an approach may provide a novel venue for treating clinical pain conditions. | Zhang HX, Hyrc K, Thio LL (2009) The glycine transport inhibitor sarcosine is an NMDA receptor co-agonist that differs from glycine. The Journal of physiology 587, 3207-3220 [PubMed:19433577] [show Abstract] Sarcosine is an amino acid involved in one-carbon metabolism and a promising therapy for schizophrenia because it enhances NMDA receptor (NMDAR) function by inhibiting glycine uptake. The structural similarity between sarcosine and glycine led us to hypothesize that sarcosine is also an agonist like glycine. We examined this possibility using whole-cell recordings from cultured embryonic mouse hippocampal neurons. We found that sarcosine is an NMDAR co-agonist at the glycine binding site. However, sarcosine differed from glycine because less NMDAR desensitization occurred with sarcosine than with glycine as the co-agonist. This finding led us to examine whether the physiological effects of NMDAR activation with these two co-agonists are the same. The difference in desensitization probably accounts for rises in intracellular Ca(2+), as assessed by the fluorescent indicator fura-FF, being larger when NMDAR activation occurred with sarcosine than with glycine. In addition, Ca(2+)-activated K(+) currents following NMDAR activation were larger with sarcosine than with glycine. Compared to glycine, NMDAR-mediated autaptic currents decayed faster with sarcosine suggesting that NMDAR deactivation also differs with these two co-agonists. Despite these differences, NMDAR-dependent neuronal death as assessed by propidium iodide was similar with both co-agonists. The same was true for neuronal bursting. Thus, sarcosine may enhance NMDAR function by more than one mechanism and may have different effects from other NMDAR co-agonists. | Shim SS, Hammonds MD, Kee BS (2008) Potentiation of the NMDA receptor in the treatment of schizophrenia: focused on the glycine site. European archives of psychiatry and clinical neuroscience 258, 16-27 [PubMed:17901997] [show Abstract] N-methyl-D-aspartate receptor (NMDAR) hypo-function theory of schizophrenia proposes that impairment in NMDAR function be associated with the pathophysiology of schizophrenia and suggests that enhancement of the receptor function may produce efficacy for schizophrenia. Consistent with this theory, for the last decade, clinical trials have demonstrated that the enhancement of NMDAR function by potentiating the glycine site of the receptor is efficacious in the treatment of schizophrenia. Full agonists of the glycine site, glycine and D-serine and a glycine transporter-1 inhibitor, sarcosine, added to antipsychotic drugs, have been shown to be effective in the treatment of negative symptoms and possibly cognitive symptoms without significantly affecting the positive symptoms of schizophrenia. A partial agonist of the glycine site, D-cycloserine, added to antipsychotic drugs, can be effective for the negative symptoms at the therapeutic doses. However, these drugs have not shown clinical efficacy when added to clozapine, suggesting that the interactions of clozapine and the glycine site potentiators may be different from those of other antipsychotic drugs and the potentiators. This article suggests that the glycine site potentiators may produce efficacy for negative and cognitive symptoms by blocking apoptosis-like neuropathological processes in patients with chronic schizophrenia and thereby can deter progressive deterioration of the disorder. This article proposes a polypharmacy of glycine site potentiators augmented with antipsychotic drugs to control positive and negative symptoms in a synergistic manner and block deterioration in schizophrenia. Since the NMDAR complex consists of multiple sites modulating receptor functions, the efficacy of glycine site potentiators for schizophrenia suggests the possibility that manipulation of other modulating sites of the NMDAR can also be efficacious in the treatment of schizophrenia. | Salek RM, Maguire ML, Bentley E, Rubtsov DV, Hough T, Cheeseman M, Nunez D, Sweatman BC, Haselden JN, Cox RD, Connor SC, Griffin JL (2007) A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human. Physiological genomics 29, 99-108 [PubMed:17190852] [show Abstract] Type 2 diabetes mellitus is the result of a combination of impaired insulin secretion with reduced insulin sensitivity of target tissues. There are an estimated 150 million affected individuals worldwide, of whom a large proportion remains undiagnosed because of a lack of specific symptoms early in this disorder and inadequate diagnostics. In this study, NMR-based metabolomic analysis in conjunction with multivariate statistics was applied to examine the urinary metabolic changes in two rodent models of type 2 diabetes mellitus as well as unmedicated human sufferers. The db/db mouse and obese Zucker (fa/fa) rat have autosomal recessive defects in the leptin receptor gene, causing type 2 diabetes. 1H-NMR spectra of urine were used in conjunction with uni- and multivariate statistics to identify disease-related metabolic changes in these two animal models and human sufferers. This study demonstrates metabolic similarities between the three species examined, including metabolic responses associated with general systemic stress, changes in the TCA cycle, and perturbations in nucleotide metabolism and in methylamine metabolism. All three species demonstrated profound changes in nucleotide metabolism, including that of N-methylnicotinamide and N-methyl-2-pyridone-5-carboxamide, which may provide unique biomarkers for following type 2 diabetes mellitus progression. | Tsai GE, Yang P, Chang YC, Chong MY (2006) D-alanine added to antipsychotics for the treatment of schizophrenia. Biological psychiatry 59, 230-234 [PubMed:16154544] [show Abstract]
BackgroundHypofunction of the N-methyl-d-aspartate (NMDA) subtype glutamate receptor had been implicated in the pathophysiology of schizophrenia. Treatment with D-serine, glycine, endogenous full agonists of the glycine site of the NMDA receptor (NMDA-glycine site), D-cycloserine, a partial agonist, or sarcosine, a glycine transporter-1 inhibitor, improves the symptoms of schizophrenia. D-alanine is another endogenous agonist of the NMDA-glycine site that might have beneficial effects on schizophrenia.MethodsThirty-two schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-alanine (100 mg/kg/day), which was added to their stable antipsychotic regimens. Measures of clinical efficacy and side effects were determined every other week.ResultsPatint who received D-alanine treatment revealed significant reductions in their Clinical Global Impression Scale and Positive and Negative Syndrome Scale (PANSS) total scores. The Scale for the Assessment of Negative Symptoms and PANSS subscores of positive and cognitive symptoms were improved. D-alanine was well tolerated, and no significant side effect was noted.ConclusionsThe significant improvement with the D-alanine further supports the hypothesis of hypofunction of NMDA neurotransmission in schizophrenia and strengthens the proof of the principle that NMDA-enhancing treatment is a promising approach for the pharmacotherapy of schizophrenia. | Deutsch SI, Rosse RB, Long KD, Gaskins B, Mastropaolo J (2006) Rare neurodevelopmental abnormalities of sarcosinemia may involve glycinergic stimulation of a primed N-methyl-d-aspartate receptor. Clinical neuropharmacology 29, 361-363 [PubMed:17095900] [show Abstract] Sarcosinemia is a relatively rare autosomal recessive disorder that has a varied phenotypic presentation; rarely, it is associated with neurodevelopmental and neurological abnormalities. Sarcosine is a key intermediate in 1-carbon metabolism, and its elevation in blood and urine could reflect a deficient pool size of activated 1-carbon units. Sarcosine is also an inhibitor of an important glycine transporter in brain and is under clinical investigation as a glycinergic intervention for conditions with presumed N-methyl-d-aspartate (NMDA) receptor hypofunction, such as schizophrenia. Preclinical research with a mouse model that is used to study pharmacological modulation of endogenous NMDA receptor-mediated tone may clarify, at least in some instances, varied phenotypic presentations of sarcosinemia that are often clinically benign. Sarcosine's effectiveness as a glycinergic agonist intervention for NMDA receptor hypofunction depends on an interaction between genetic background and a stressful environmental insult. Thus, neurodevelopmental and neurological abnormalities may manifest rarely in sarcosinemia in the context of relatively unique genetic factors and fetal insult or stress. | Tsai G, Lane HY, Yang P, Chong MY, Lange N (2004) Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia. Biological psychiatry 55, 452-456 [PubMed:15023571] [show Abstract]
BackgroundHypofunction of N-methyl-D-aspartate glutamate receptor had been implicated in the pathophysiology of schizophrenia. Treatment with D-serine or glycine, endogenous full agonists of the glycine site of N-methyl-D-aspartate receptor, or D-cycloserine, a partial agonist, improve the symptoms of schizophrenia. N-methylglycine (sarcosine) is an endogenous antagonist of glycine transporter-1, which potentiates glycine's action on N-methyl-D-aspartate glycine site and can have beneficial effects on schizophrenia.MethodsThirty-eight schizophrenic patients were enrolled in a 6-week double-blind, placebo-controlled trial of sarcosine (2 g/d), which was added to their stable antipsychotic regimens. Twenty of them received risperidone. Measures of clinical efficacy and side effects were determined every other week.ResultsPatient who received sarcosine treatment revealed significant improvements in their positive, negative, cognitive, and general psychiatric symptoms. Similar therapeutic effects were observed when only risperidone-treated patients were analyzed. Sarcosine was well-tolerated, and no significant side effect was noted.ConclusionsSarcosine treatment can benefit schizophrenic patients treated by antipsychotics including risperidone. The significant improvement with the sarcosine further supports the hypothesis of N-methyl-D-aspartate receptor hypofunction in schizophrenia. Glycine transporter-1 is a novel target for the pharmacotherapy to enhance N-methyl-D-aspartate function. | Huang H, Barakat L, Wang D, Bordey A (2004) Bergmann glial GlyT1 mediates glycine uptake and release in mouse cerebellar slices. The Journal of physiology 560, 721-736 [PubMed:15331688] [show Abstract] Glycine is an inhibitory neurotransmitter and is critical for NMDA receptor activation. These roles are dependent on extracellular glycine levels, which are regulated by Na(+)/Cl(-)-dependent glycine transporters (GlyTs) in neurones and glia. The glial GlyT subtype GlyT1 is well located to activate NMDA receptors. However, glial GlyTs have not been studied in an intact system thus far. Whole-cell patch-clamp recordings were obtained from Bergmann glia in mice cerebellar slices to determine whether these glia express functional GlyT1 that can mediate both glycine uptake and efflux. In the presence of a glycine receptor blocker, glycine and a substrate agonist for GlyT1, sarcosine, induced voltage-dependent inward currents that were abolished by removing external Na(+), identifying them as transport currents. Inhibitors of glycine transport through GlyT1 (sarcosine and (N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS)) reduced glycine currents by approximately 85%, consistent with positive immunostaining for GlyT1 in Bergmann glia while inhibitors of glycine transport through GlyT2 (4-benzyloxy-3,5-dimethoxy-N-[1-(dimethylaminocyclopently)methyl]benzamide (ORG 25543) and amoxapine) or through systems A and ASC did not affect glycine transport currents. Following internal glycine perfusion during the recording, outward currents progressively developed at -50 mV and external glycine-induced uptake currents were reduced. Using paired recordings of a Bergmann glial cell and a granule cell in the whole cell and outside-out modes, respectively, depolarizations of Bergmann glia to +20 mV induced a 73% increase in the open probability of glycine receptor channels in membrane patches of granule cells. This increase was prevented when NFPS was included in the bath solution. Overall, these results demonstrate for the first time that Bergmann glia express functional GlyT1 that can work in reverse at near-physiological ionic and internal glycine conditions in brain slices. These glial GlyTs can probably mediate glycine efflux under conditions of metabolic impairments like ischaemia. | Mori M, Gähwiler BH, Gerber U (2002) Beta-alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro. The Journal of physiology 539, 191-200 [PubMed:11850512] [show Abstract] Electrophysiological and pharmacological properties of glycine receptors were characterized in hippocampal organotypic slice cultures. In the presence of ionotropic glutamate and GABA(B) receptor antagonists, pressure-application of glycine onto CA3 pyramidal cells induced a current associated with increased chloride conductance, which was inhibited by strychnine. Similar chloride currents could also be induced with beta-alanine or taurine. Whole-cell glycine responses were significantly greater in CA3 pyramidal cells than in CA1 pyramidal cells and dentate granule cells, while responses to GABA were similar among these three cell types. Although these results demonstrate the presence of functional glycine receptors in the hippocampus, no evidence for their activation during synaptic stimulation was found. Gabazine, a selective GABA(A) receptor antagonist, totally blocked evoked IPSCs in CA3 pyramidal cells. Glycine receptor activation is not dependent on transporter-controlled levels of extracellular glycine, as no chloride current was observed in response to sarcosine, an inhibitor of glycine transporters. In contrast, application of guanidinoethanesulfonic acid, an uptake inhibitor of beta-alanine and taurine, induced strychnine-sensitive chloride current in the presence of gabazine. These data indicate that modulation of transporters for the endogenous amino acids, beta-alanine and taurine, can regulate tonic activation of glycine receptors, which may function in maintenance of inhibitory tone in the hippocampus. | Gederaas OA, Holroyd A, Brown SB, Vernon D, Moan J, Berg K (2001) 5-Aminolaevulinic acid methyl ester transport on amino acid carriers in a human colon adenocarcinoma cell line. Photochemistry and photobiology 73, 164-169 [PubMed:11272730] [show Abstract] The transport mechanisms of 5-aminolevulinic acid methyl ester (5-ALA-ME) have been studied in a human adenocarcinoma cell line (WiDr) by means of 14[C]-labeled 5-ALA-ME. The transport was found to be partly Na+ dependent, while the extracellular Cl- concentration did not affect the uptake. The transport of 5-ALA-ME into WiDr cells was dependent on the incubation temperature and was found to be completely blocked by the inhibitors of energy metabolism, 2-deoxyglucose and sodium azide. WiDr cells were treated with 10 mM of 14 different amino acids and the substrate specificity of the 5-ALA-ME transporter(s) was analyzed by treating the cells with 23 microM or 1 mM 14[C]-labeled 5-ALA-ME. The transport of 5-ALA-ME was found to be inhibited to the highest extent, i.e. about 60%, by the nonpolar amino acids L-alanine, L-methionine, L-tryptophan and glycine. The uptake of 5-ALA-ME followed an exponential decay with increasing concentration of glycine, reaching a maximum inhibition of uptake of 5-ALA-ME of 55%. Sarcosine, a specific inhibitor of system Gly, did not significantly inhibit 5-ALA-ME transport. In contrast to transport of 5-ALA, 5-ALA-ME does not seem to be taken up by system BETA transporters. In conclusion, the cellular uptake of 5-ALA-ME into WiDr cells seems to be due to active transport mechanisms, involving transporters of nonpolar amino acids. |
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