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<h1 id="firstHeading" class="firstHeading mw-first-heading"><span class="mw-page-title-main">SNAT3</span></h1>
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<div id="mw-content-text" class="mw-body-content mw-content-ltr" lang="de" dir="ltr"><div class="mw-content-ltr mw-parser-output" lang="de" dir="ltr"><p><b>SNAT3</b> oder <a href="SLC-Transporter" title="SLC-Transporter">SLC38A3</a> wurde früher als <i>S</i>ystem <i>N</i> (SN1)- oder NAT-Transporter bezeichnet. Die ursprüngliche Benennung beruhte auf der Substratspezifität, da SNAT3 <i>n</i>eutrale <i>A</i>minosäuren <i>t</i>ransportiert, die eine Stickstoffgruppe (chemisches Symbol <a href="Stickstoff" title="Stickstoff">N</a>) in ihrem Rest tragen. SNAT3 kommt hauptsächlich in der Leber vor, wo er zu Synthese von <a href="Harnstoff" title="Harnstoff">Harnstoff</a> Glutamin bereitstellt, aber er ist auch im Gehirn<sup id="cite_ref-pmid12059969_1-0" class="reference"><a href="#cite_note-pmid12059969-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> und in den Nieren<sup id="cite_ref-pmid17003226_2-0" class="reference"><a href="#cite_note-pmid17003226-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> nachweisbar.
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<div class="mw-heading mw-heading2"><h2 id="Nomenklatur">Nomenklatur</h2></div>
<p>Im Zuge der <a href="Genom" title="Genom">Genomentschlüsselung</a> wurden die früher mutwillig vergebenen Proteinbenennungen für SNAT3 auf Grund von <a href="Homologie_(Biologie)" title="Homologie (Biologie)">Homologie</a> in Genfamilien unterteilt. Die Proteine werden heute entweder nur noch mit der Kurzform der Genfamilie genannt, oder mit einer einheitlichen Kurzfassung, die im Zusammenhang mit ihren Eigenschaften steht.
</p>
<div class="mw-heading mw-heading2"><h2 id="Eigenschaften">Eigenschaften</h2></div>
<p>SNAT3 ist ein natriumanbhängiger, neutraler <a href="Aminos%C3%A4ure" class="mw-redirect" title="Aminosäure">Aminosäure</a>-Transporter, der hauptsächlich das für den Menschen sehr wichtige <a href="Glutamin" title="Glutamin">Glutamin</a>, aber auch <a href="Asparagin" title="Asparagin">Asparagin</a> und <a href="Histidin" title="Histidin">Histidin</a>, transportiert. Die Stöchiometrie ist 1 Na+:1Gln im Symport, 1H+ im Antiport, womit rechnerisch ein elektroneutraler Transport entsteht.<sup id="cite_ref-pmid11850497_3-0" class="reference"><a href="#cite_note-pmid11850497-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> Im Expressionssystem <i>Xenopus</i> Oozyte zeigt SNAT3 während des Aminosäuretransports jedoch eine Kationen-Einwärtsleitfähigkeit.<sup id="cite_ref-pmid17148440_4-0" class="reference"><a href="#cite_note-pmid17148440-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> Diese Leitfähigkeit erweist sich als sensitiv für <a href="Carboanhydrase" class="mw-redirect" title="Carboanhydrase">Carboanhydrase</a> II, die die Glutamin-induzierte Leitfähigkeit unterdrückt, wenn sie katalytisch aktiv ist.<sup id="cite_ref-pmid17664347_5-0" class="reference"><a href="#cite_note-pmid17664347-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup>
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<div class="mw-heading mw-heading2"><h2 id="Pathologie">Pathologie</h2></div>
<p>SNAT3-knock-out Mäuse sind nicht länger als 14 Tage postnatal überlebensfähig. Da ein weiterer System N Transporter, SNAT5, in Gehirn<sup id="cite_ref-pmid15390093_6-0" class="reference"><a href="#cite_note-pmid15390093-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> und Leber<sup id="cite_ref-pmid15218073_7-0" class="reference"><a href="#cite_note-pmid15218073-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> existiert und kein Inhibitor für SNAT3 auf dem Markt ist, konnte bislang keine eindeutige Abhängigkeit z.&nbsp;B. der hepatischen Enzephalopathie von der Aktivität von SNAT3 nachgewiesen werden.
SNAT3 ist jedoch durch den Protonen-<a href="Antiport" class="mw-redirect" title="Antiport">Membrantransport</a> ein Säure/Base-Transporter und trägt damit zur <a href="PH-Wert" title="PH-Wert">pH-Wert</a>-Homöostase bei. Er wird nachweislich bei <a href="Azidose" title="Azidose">Azidose</a> in seiner Gewebsexpression verändert. Dies konnte für die Nieren in Form einer Hochregulation<sup id="cite_ref-pmid19458124_8-0" class="reference"><a href="#cite_note-pmid19458124-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> und für in Zellkultur befindliche Gliomazellen in Form einer Herabregulation<sup id="cite_ref-pmid16513216_9-0" class="reference"><a href="#cite_note-pmid16513216-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> nachgewiesen werden.
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<div class="mw-heading mw-heading2"><h2 id="Quellen">Quellen</h2></div>
<ol class="references">
<li id="cite_note-pmid12059969-1"><span class="mw-cite-backlink"><a href="#cite_ref-pmid12059969_1-0">↑</a></span> <span class="reference-text">Boulland JL, Osen KK, Levy LM, Danbolt NC, Edwards RH, Storm-Mathisen J, Chaudhry FA: <cite style="font-style:italic">Cell-specific expression of the glutamine transporter SN1 suggests differences in dependence on the glutamine cycle</cite>. In: <cite style="font-style:italic">Eur J Neurosci</cite>. 15. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em">&nbsp;</span>10</span>, 2002, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em">&nbsp;</span>1615–1631</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1046/j.1460-9568.2002.01995.x">10.1046/j.1460-9568.2002.01995.x</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/12059969?dopt=Abstract">PMID 12059969</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rfr_id=info:sid/de.wikipedia.org:SNAT3&amp;rft.atitle=Cell-specific+expression+of+the+glutamine+transporter+SN1+suggests+differences+in+dependence+on+the+glutamine+cycle&amp;rft.au=Boulland+JL%2C+Osen+KK%2C+Levy+LM%2C+...&amp;rft.date=2002&amp;rft.doi=10.1046%2Fj.1460-9568.2002.01995.x&amp;rft.genre=journal&amp;rft.issue=10&amp;rft.jtitle=Eur+J+Neurosci&amp;rft.pages=1615-1631&amp;rft.pmid=12059969&amp;rft.volume=15.+Jahrgang" style="display:none">&nbsp;</span></span>
</li>
<li id="cite_note-pmid17003226-2"><span class="mw-cite-backlink"><a href="#cite_ref-pmid17003226_2-0">↑</a></span> <span class="reference-text">Moret C, Dave MH, Schulz N, Jiang JX, Verrey F, Wagner CA.: <cite style="font-style:italic">Regulation of renal amino acid transporters during metabolic acidosis.</cite> In: <cite style="font-style:italic">Am J Physiol Renal Physiol</cite>. 292. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em">&nbsp;</span>2</span>, 2007, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em">&nbsp;</span>F555–66</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1152/ajprenal.00113.2006">10.1152/ajprenal.00113.2006</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/17003226?dopt=Abstract">PMID 17003226</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rfr_id=info:sid/de.wikipedia.org:SNAT3&amp;rft.atitle=Regulation+of+renal+amino+acid+transporters+during+metabolic+acidosis.&amp;rft.au=Moret+C%2C+Dave+MH%2C+Schulz+N%2C+...&amp;rft.date=2007&amp;rft.doi=10.1152%2Fajprenal.00113.2006&amp;rft.genre=journal&amp;rft.issue=2&amp;rft.jtitle=Am+J+Physiol+Renal+Physiol&amp;rft.pages=F555-66&amp;rft.pmid=17003226&amp;rft.volume=292.+Jahrgang" style="display:none">&nbsp;</span></span>
</li>
<li id="cite_note-pmid11850497-3"><span class="mw-cite-backlink"><a href="#cite_ref-pmid11850497_3-0">↑</a></span> <span class="reference-text">Bröer A, Albers A, Setiawan I, Edwards RH, Chaudhry FA, Lang F, Wagner CA, Bröer S: <cite style="font-style:italic">Regulation of the glutamine transporter SN1 by extracellular pH and intracellular sodium ions.</cite> In: <cite style="font-style:italic">J Physiol</cite>. 15. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em">&nbsp;</span>539</span>, 2002, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em">&nbsp;</span>3–14</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1113/jphysiol.2001.013303">10.1113/jphysiol.2001.013303</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/11850497?dopt=Abstract">PMID 11850497</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rfr_id=info:sid/de.wikipedia.org:SNAT3&amp;rft.atitle=Regulation+of+the+glutamine+transporter+SN1+by+extracellular+pH+and+intracellular+sodium+ions.&amp;rft.au=Br%C3%B6er+A%2C+Albers+A%2C+Setiawan+I%2C+...&amp;rft.date=2002&amp;rft.doi=10.1113%2Fjphysiol.2001.013303&amp;rft.genre=journal&amp;rft.issue=539&amp;rft.jtitle=J+Physiol&amp;rft.pages=3-14&amp;rft.pmid=11850497&amp;rft.volume=15.+Jahrgang" style="display:none">&nbsp;</span></span>
</li>
<li id="cite_note-pmid17148440-4"><span class="mw-cite-backlink"><a href="#cite_ref-pmid17148440_4-0">↑</a></span> <span class="reference-text">Schneider HP, Bröer S, Bröer A, Deitmer JW: <cite style="font-style:italic">Heterologous expression of the glutamine transporter SNAT3 in Xenopus oocytes is associated with four modes of uncoupled transport.</cite> In: <cite style="font-style:italic"><a href="J_Biol_Chem" class="mw-redirect" title="J Biol Chem">J Biol Chem</a></cite>. 282. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em">&nbsp;</span>6</span>, 2007, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em">&nbsp;</span>3788–3798</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1074/jbc.M609452200">10.1074/jbc.M609452200</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/17148440?dopt=Abstract">PMID 17148440</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rfr_id=info:sid/de.wikipedia.org:SNAT3&amp;rft.atitle=Heterologous+expression+of+the+glutamine+transporter+SNAT3+in+Xenopus+oocytes+is+associated+with+four+modes+of+uncoupled+transport.&amp;rft.au=Schneider+HP%2C+Br%C3%B6er+S%2C+Br%C3%B6er+A%2C+...&amp;rft.date=2007&amp;rft.doi=10.1074%2Fjbc.M609452200&amp;rft.genre=journal&amp;rft.issue=6&amp;rft.jtitle=J+Biol+Chem&amp;rft.pages=3788-3798&amp;rft.pmid=17148440&amp;rft.volume=282.+Jahrgang" style="display:none">&nbsp;</span></span>
</li>
<li id="cite_note-pmid17664347-5"><span class="mw-cite-backlink"><a href="#cite_ref-pmid17664347_5-0">↑</a></span> <span class="reference-text">Weise A, Becker HM, Deitmer JW: <cite style="font-style:italic">Enzymatic suppression of the membrane conductance associated with the glutamine transporter SNAT3 expressed in <i>Xenopus</i> oocytes by carbonic anhydrase II.</cite> In: <cite style="font-style:italic"><a href="J_Gen_Physiol" class="mw-redirect" title="J Gen Physiol">J Gen Physiol</a></cite>. 130. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em">&nbsp;</span>2</span>, 2007, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em">&nbsp;</span>203–215</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1085/jgp.200709809">10.1085/jgp.200709809</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/17664347?dopt=Abstract">PMID 17664347</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rfr_id=info:sid/de.wikipedia.org:SNAT3&amp;rft.atitle=Enzymatic+suppression+of+the+membrane+conductance+associated+with+the+glutamine+transporter+SNAT3+expressed+in+Xenopus+oocytes+by+carbonic+anhydrase+II.&amp;rft.au=Weise+A%2C+Becker+HM%2C+Deitmer+JW&amp;rft.date=2007&amp;rft.doi=10.1085%2Fjgp.200709809&amp;rft.genre=journal&amp;rft.issue=2&amp;rft.jtitle=J+Gen+Physiol&amp;rft.pages=203-215&amp;rft.pmid=17664347&amp;rft.volume=130.+Jahrgang" style="display:none">&nbsp;</span></span>
</li>
<li id="cite_note-pmid15390093-6"><span class="mw-cite-backlink"><a href="#cite_ref-pmid15390093_6-0">↑</a></span> <span class="reference-text">Cubelos B, González-González IM, Giménez C, Zafra F: <cite style="font-style:italic">Amino acid transporter SNAT5 localizes to glial cells in the rat brain.</cite> In: <cite style="font-style:italic">Glia</cite>. 49. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em">&nbsp;</span>2</span>, 2005, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em">&nbsp;</span>230–244</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1002/glia.20106">10.1002/glia.20106</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/15390093?dopt=Abstract">PMID 15390093</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rfr_id=info:sid/de.wikipedia.org:SNAT3&amp;rft.atitle=Amino+acid+transporter+SNAT5+localizes+to+glial+cells+in+the+rat+brain.&amp;rft.au=Cubelos+B%2C+Gonz%C3%A1lez-Gonz%C3%A1lez+IM%2C+Gim%C3%A9nez+C%2C+...&amp;rft.date=2005&amp;rft.doi=10.1002%2Fglia.20106&amp;rft.genre=journal&amp;rft.issue=2&amp;rft.jtitle=Glia&amp;rft.pages=230-244&amp;rft.pmid=15390093&amp;rft.volume=49.+Jahrgang" style="display:none">&nbsp;</span></span>
</li>
<li id="cite_note-pmid15218073-7"><span class="mw-cite-backlink"><a href="#cite_ref-pmid15218073_7-0">↑</a></span> <span class="reference-text">Baird FE, Beattie KJ, Hyde AR, Ganapathy V, Rennie MJ, Taylor PM: <cite style="font-style:italic">Bidirectional substrate fluxes through the system N (SNAT5) glutamine transporter may determine net glutamine flux in rat liver.</cite> In: <cite style="font-style:italic">J Physiol</cite>. 559. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em">&nbsp;</span>2</span>, 2004, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em">&nbsp;</span>367–381</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1113/jphysiol.2003.060293">10.1113/jphysiol.2003.060293</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/15218073?dopt=Abstract">PMID 15218073</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rfr_id=info:sid/de.wikipedia.org:SNAT3&amp;rft.atitle=Bidirectional+substrate+fluxes+through+the+system+N+%28SNAT5%29+glutamine+transporter+may+determine+net+glutamine+flux+in+rat+liver.&amp;rft.au=Baird+FE%2C+Beattie+KJ%2C+Hyde+AR%2C+...&amp;rft.date=2004&amp;rft.doi=10.1113%2Fjphysiol.2003.060293&amp;rft.genre=journal&amp;rft.issue=2&amp;rft.jtitle=J+Physiol&amp;rft.pages=367-381&amp;rft.pmid=15218073&amp;rft.volume=559.+Jahrgang" style="display:none">&nbsp;</span></span>
</li>
<li id="cite_note-pmid19458124-8"><span class="mw-cite-backlink"><a href="#cite_ref-pmid19458124_8-0">↑</a></span> <span class="reference-text">Busque SM, Wagner CA: <cite style="font-style:italic">Potassium restriction, high protein intake, and metabolic acidosis increase expression of the glutamine transporter SNAT3 (Slc38a3) in mouse kidney.</cite> In: <cite style="font-style:italic"><a href="Am_J_Physiol-Renal_Physiol" class="mw-redirect" title="Am J Physiol-Renal Physiol">Am J Physiol-Renal Physiol</a></cite>. 297. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em">&nbsp;</span>2</span>, 2009, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em">&nbsp;</span>F440-F450</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1152/ajprenal.90318.2008">10.1152/ajprenal.90318.2008</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/19458124?dopt=Abstract">PMID 19458124</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rfr_id=info:sid/de.wikipedia.org:SNAT3&amp;rft.atitle=Potassium+restriction%2C+high+protein+intake%2C+and+metabolic+acidosis+increase+expression+of+the+glutamine+transporter+SNAT3+%28Slc38a3%29+in+mouse+kidney.&amp;rft.au=Busque+SM%2C+Wagner+CA&amp;rft.date=2009&amp;rft.doi=10.1152%2Fajprenal.90318.2008&amp;rft.genre=journal&amp;rft.issue=2&amp;rft.jtitle=Am+J+Physiol-Renal+Physiol&amp;rft.pages=F440-F450&amp;rft.pmid=19458124&amp;rft.volume=297.+Jahrgang" style="display:none">&nbsp;</span></span>
</li>
<li id="cite_note-pmid16513216-9"><span class="mw-cite-backlink"><a href="#cite_ref-pmid16513216_9-0">↑</a></span> <span class="reference-text">Sidoryk M, Obara M, Albrecht J: <cite style="font-style:italic">Selective decrease of SN1(SNAT3) mRNA expression in human and rat glioma cells adapted to grow in acidic medium.</cite> In: <cite style="font-style:italic">Neurochem Int</cite>. 48. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em">&nbsp;</span>6–7</span>, 2006, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em">&nbsp;</span>547–552</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1016/j.neuint.2005.12.026">10.1016/j.neuint.2005.12.026</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/16513216?dopt=Abstract">PMID 16513216</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rfr_id=info:sid/de.wikipedia.org:SNAT3&amp;rft.atitle=Selective+decrease+of+SN1%28SNAT3%29+mRNA+expression+in+human+and+rat+glioma+cells+adapted+to+grow+in+acidic+medium.&amp;rft.au=Sidoryk+M%2C+Obara+M%2C+Albrecht+J&amp;rft.date=2006&amp;rft.doi=10.1016%2Fj.neuint.2005.12.026&amp;rft.genre=journal&amp;rft.issue=6-7&amp;rft.jtitle=Neurochem+Int&amp;rft.pages=547-552&amp;rft.pmid=16513216&amp;rft.volume=48.+Jahrgang" style="display:none">&nbsp;</span></span>
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