Disease relevance of SLC17A6

• By contrast, VGLUT2 was present in horizontal cells and ganglion cells in rat and human retina [1].
• Here, we show that platelets express the pre-synaptic markers VGLUT1 and VGLUT2 and release glutamate following aggregation, implying a possible contributory role in the pathophysiology of stroke, migraine, and other excitotoxic disorders [2].
• Confocal analysis of spinal cord sections at 8 weeks-12 months after ischemia revealed a continuing presence of ChAT positive alpha-motoneurons, Ia afferents and VGLUT2 and VGLUT1-positive terminals but a selective loss of small presumably inhibitory interneurons between laminae V-VII [3].

High impact information on SLC17A6

• VGLUT3 also differs from VGLUT1 and VGLUT2 in its subcellular location, with somatodendritic as well as axonal expression [4].
• Thus, VGLUT2 appears to possess two intrinsic transport machineries that are independent of each other: a DeltaPsi-dependent l-glutamate uptake and a Na(+)-dependent P(i) uptake [5].
• The predicted amino acid sequence of hVGLUT3 shows 72% identity to both hVGLUT1 and hVGLUT2. hVGLUT3 functions as a vesicular glutamate transporter with similar properties to the other isoforms when it is heterologously expressed in a neuroendocrine cell line [6].
• In contrast, DNPI mRNA is expressed at low levels in cerebellum and hippocampus, where BNPI mRNA is expressed at high levels [7].
• Northern blot analysis shows that DNPI mRNA is expressed predominantly in brain, where the highest levels are observed in medulla, substantia nigra, subthalamic nucleus, and thalamus, all of which express BNPI mRNA at low levels [7].

Biological context of SLC17A6

• Assignment of SLC17A6 (alias DNPI), the gene encoding brain/pancreatic islet-type Na+-dependent inorganic phosphate cotransporter to human chromosome 11p14.3 [8].
• The distribution of VGLUT1 and VGLUT2 accounts for the ability of most established excitatory neurons to release glutamate by exocytosis [4].
• The results indicate both that cerebellar granule cells are mature at approximately 7 days in vitro, and that the up-regulation of VGLUT1 and down-regulation of VGLUT2 in cerebellar granule cells are both independent of surrounding astrocytes and neuronal input [9].

Anatomical context of SLC17A6

• In human retina, VGLUT2 was also found in some amacrine cells, including GAD-immunopositive amacrine cells [1].
• No hybridizing signal for DNPI mRNA is observed in the glia-rich region of corpus callosum [7].
• Expression of DNPI mRNA in Xenopus oocytes resulted in a significant increase in Na(+)-dependent P(i) transport, indicating that DNPI is a novel Na(+)/P(i) cotransporter [7].
• In the forebrain, VGLUT2 signals were demonstrated in half of the A11 TH-labeled neurons in the hypothalamus [10].
• In the present study, we examined expression of vesicular glutamate transporters (VGLUTs), VGLUT1 and VGLUT2, in the primary afferent neurons of the Vmes (Vmes neurons) in neonatal and adult rats [11].

Associations of SLC17A6 with chemical compounds

• Recently, two mammalian isoforms of a vesicular glutamate transporter, VGLUT1 and VGLUT2, have been identified, the expression of which enables quantal release of glutamate from glutamatergic neurons [6].
• This increase in VGLUT2 mRNA was suppressed by actinomycin D [12].
• VGLUT2 mRNA was significantly increased in beta- and alpha-cells by high and low glucose concentration, respectively [12].
• These results indicate that VGLUT2 is expressed in subsets of A10 and A11 dopamine neurons, which might release dopamine and glutamate separately from different varicosities in the majority of their single axons [10].
• Third, the recent cloning of 3 vesicular glutamate transporters (VGLUT1-3) has led to the discovery that noradrenergic neurons contain VGLUT2 mRNA, whereas 5-HT neurons contain VGLUT3 mRNA [13].

Regulatory relationships of SLC17A6

• Northern blot and in situ hybridization analyses indicate that DNPI mRNA is expressed in some brain regions in which VGLUT1 mRNA is not expressed [14].

Other interactions of SLC17A6

• Although mammalian VGLUT1 and VGLUT2 exhibit a complementary expression pattern covering all glutamatergic pathways in the CNS, expression of hVGLUT3 overlaps with them in some brain areas, suggesting molecular diversity that may account for physiological heterogeneity in glutamatergic synapses [6].
• Reverse-transcriptase polymerase chain reaction analysis detected full-length VGLUT2 gene transcripts in the ventral midbrain [10].
• A quantitative method is described for the measurement of N-mononitrosopiperazine (NPIP) and N,N'-dinitrosopiperazine (DNPIP) in drug formulations containing piperazine, using a gas chromatograph interfaced to a thermal energy analyzer (GC/TEA) [15].
• The intraepithelial vagal sensory innervation of NEBs, on the other hand, appears to be myelinated and could be labelled by antibodies against VGLUT1, VGLUT2, CB and P2X3 receptors [16].

Analytical, diagnostic and therapeutic context of SLC17A6

• In the ventral midbrain, in situ hybridization analysis revealed no VGLUT1 mRNA expression, a widespread but discrete pattern of VGLUT2 mRNA expression, and a highly limited expression of VGLUT3 mRNA [10].
• The magnetization subtraction technique (MS), which is equivalent to the inversion recovery technique in strong magnetic fields, has been implemented in dynamic nuclear polarization-enhanced magnetic resonance imaging (DNPI) [17].

References