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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Rabbit sucrase-isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A.</title>
<author><name sortKey="Pothoulakis, C" sort="Pothoulakis, C" uniqKey="Pothoulakis C" first="C" last="Pothoulakis">C. Pothoulakis</name>
</author>
<author><name sortKey="Gilbert, R J" sort="Gilbert, R J" uniqKey="Gilbert R" first="R J" last="Gilbert">R J Gilbert</name>
</author>
<author><name sortKey="Cladaras, C" sort="Cladaras, C" uniqKey="Cladaras C" first="C" last="Cladaras">C. Cladaras</name>
</author>
<author><name sortKey="Castagliuolo, I" sort="Castagliuolo, I" uniqKey="Castagliuolo I" first="I" last="Castagliuolo">I. Castagliuolo</name>
</author>
<author><name sortKey="Semenza, G" sort="Semenza, G" uniqKey="Semenza G" first="G" last="Semenza">G. Semenza</name>
</author>
<author><name sortKey="Hitti, Y" sort="Hitti, Y" uniqKey="Hitti Y" first="Y" last="Hitti">Y. Hitti</name>
</author>
<author><name sortKey="Montcrief, J S" sort="Montcrief, J S" uniqKey="Montcrief J" first="J S" last="Montcrief">J S Montcrief</name>
</author>
<author><name sortKey="Linevsky, J" sort="Linevsky, J" uniqKey="Linevsky J" first="J" last="Linevsky">J. Linevsky</name>
</author>
<author><name sortKey="Kelly, C P" sort="Kelly, C P" uniqKey="Kelly C" first="C P" last="Kelly">C P Kelly</name>
</author>
<author><name sortKey="Nikulasson, S" sort="Nikulasson, S" uniqKey="Nikulasson S" first="S" last="Nikulasson">S. Nikulasson</name>
</author>
<author><name sortKey="Desai, H P" sort="Desai, H P" uniqKey="Desai H" first="H P" last="Desai">H P Desai</name>
</author>
<author><name sortKey="Wilkins, T D" sort="Wilkins, T D" uniqKey="Wilkins T" first="T D" last="Wilkins">T D Wilkins</name>
</author>
<author><name sortKey="Lamont, J T" sort="Lamont, J T" uniqKey="Lamont J" first="J T" last="Lamont">J T Lamont</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">8698855</idno>
<idno type="pmc">507473</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC507473</idno>
<idno type="RBID">PMC:507473</idno>
<date when="1996">1996</date>
<idno type="wicri:Area/Pmc/Corpus">000459</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000459</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Rabbit sucrase-isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A.</title>
<author><name sortKey="Pothoulakis, C" sort="Pothoulakis, C" uniqKey="Pothoulakis C" first="C" last="Pothoulakis">C. Pothoulakis</name>
</author>
<author><name sortKey="Gilbert, R J" sort="Gilbert, R J" uniqKey="Gilbert R" first="R J" last="Gilbert">R J Gilbert</name>
</author>
<author><name sortKey="Cladaras, C" sort="Cladaras, C" uniqKey="Cladaras C" first="C" last="Cladaras">C. Cladaras</name>
</author>
<author><name sortKey="Castagliuolo, I" sort="Castagliuolo, I" uniqKey="Castagliuolo I" first="I" last="Castagliuolo">I. Castagliuolo</name>
</author>
<author><name sortKey="Semenza, G" sort="Semenza, G" uniqKey="Semenza G" first="G" last="Semenza">G. Semenza</name>
</author>
<author><name sortKey="Hitti, Y" sort="Hitti, Y" uniqKey="Hitti Y" first="Y" last="Hitti">Y. Hitti</name>
</author>
<author><name sortKey="Montcrief, J S" sort="Montcrief, J S" uniqKey="Montcrief J" first="J S" last="Montcrief">J S Montcrief</name>
</author>
<author><name sortKey="Linevsky, J" sort="Linevsky, J" uniqKey="Linevsky J" first="J" last="Linevsky">J. Linevsky</name>
</author>
<author><name sortKey="Kelly, C P" sort="Kelly, C P" uniqKey="Kelly C" first="C P" last="Kelly">C P Kelly</name>
</author>
<author><name sortKey="Nikulasson, S" sort="Nikulasson, S" uniqKey="Nikulasson S" first="S" last="Nikulasson">S. Nikulasson</name>
</author>
<author><name sortKey="Desai, H P" sort="Desai, H P" uniqKey="Desai H" first="H P" last="Desai">H P Desai</name>
</author>
<author><name sortKey="Wilkins, T D" sort="Wilkins, T D" uniqKey="Wilkins T" first="T D" last="Wilkins">T D Wilkins</name>
</author>
<author><name sortKey="Lamont, J T" sort="Lamont, J T" uniqKey="Lamont J" first="J T" last="Lamont">J T Lamont</name>
</author>
</analytic>
<series><title level="j">Journal of Clinical Investigation</title>
<idno type="ISSN">0021-9738</idno>
<imprint><date when="1996">1996</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>The intestinal effects of Clostridium difficile toxin A are inidated by toxin binding to luminal enterocyte receptors. We reported previously that the rabbit ileal brush border (BB) receptor is a glycoprotein with an alpha-d-galactose containing trisaccharide in the toxin-binding domain (1991. J. Clin. Invest. 88:119-125). In this study we characterized the rabbit ileal BB receptor for this toxin. Purified toxin receptor peptides of 19 and 24 amino acids showed 100% homology with rabbit sucrase-isomaltase (SI). Guinea pig receptor antiserum reacted in Western blots with rabbit SI and with the purified toxin receptor. Antireceptor IgG blocked in vitro binding of toxin A to rabbit ileal villus cell BB. Furthermore, anti-SI IgG inhibited toxin A-induced secretion (by 78.1%, P < 0.01), intestinal permeability (by 80.8%, P < 0.01), and histologic injury (P < 0.01) in rabbit ileal loops in vivo. Chinese hamster ovary cells transfected with SI cDNA showed increased intracellular calcium increase in response to native toxin (holotoxin) or to a recombinant 873-amino acid peptide representing the receptor binding domain of toxin A. These data suggest that toxin A binds specifically to carbohydrate domains on rabbit ileal SI, and that such binding is relevant to signal transduction mechanisms that mediate in vitro and in vivo toxicity.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Invest</journal-id>
<journal-title>Journal of Clinical Investigation</journal-title>
<issn pub-type="ppub">0021-9738</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">8698855</article-id>
<article-id pub-id-type="pmc">507473</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Rabbit sucrase-isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A.</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Pothoulakis</surname>
<given-names>C</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Gilbert</surname>
<given-names>R J</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Cladaras</surname>
<given-names>C</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Castagliuolo</surname>
<given-names>I</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Semenza</surname>
<given-names>G</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Hitti</surname>
<given-names>Y</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Montcrief</surname>
<given-names>J S</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Linevsky</surname>
<given-names>J</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Kelly</surname>
<given-names>C P</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Nikulasson</surname>
<given-names>S</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Desai</surname>
<given-names>H P</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Wilkins</surname>
<given-names>T D</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>LaMont</surname>
<given-names>J T</given-names>
</name>
</contrib>
</contrib-group>
<aff>Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA.</aff>
<pub-date pub-type="ppub"><day>1</day>
<month>8</month>
<year>1996</year>
</pub-date>
<volume>98</volume>
<issue>3</issue>
<fpage>641</fpage>
<lpage>649</lpage>
<abstract><p>The intestinal effects of Clostridium difficile toxin A are inidated by toxin binding to luminal enterocyte receptors. We reported previously that the rabbit ileal brush border (BB) receptor is a glycoprotein with an alpha-d-galactose containing trisaccharide in the toxin-binding domain (1991. J. Clin. Invest. 88:119-125). In this study we characterized the rabbit ileal BB receptor for this toxin. Purified toxin receptor peptides of 19 and 24 amino acids showed 100% homology with rabbit sucrase-isomaltase (SI). Guinea pig receptor antiserum reacted in Western blots with rabbit SI and with the purified toxin receptor. Antireceptor IgG blocked in vitro binding of toxin A to rabbit ileal villus cell BB. Furthermore, anti-SI IgG inhibited toxin A-induced secretion (by 78.1%, P < 0.01), intestinal permeability (by 80.8%, P < 0.01), and histologic injury (P < 0.01) in rabbit ileal loops in vivo. Chinese hamster ovary cells transfected with SI cDNA showed increased intracellular calcium increase in response to native toxin (holotoxin) or to a recombinant 873-amino acid peptide representing the receptor binding domain of toxin A. These data suggest that toxin A binds specifically to carbohydrate domains on rabbit ileal SI, and that such binding is relevant to signal transduction mechanisms that mediate in vitro and in vivo toxicity.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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