A study of PAF‐induced ocular inflammation in the rat and its inhibition by the PAF antagonist, L‐652, 731
Identifieur interne : 000844 ( Istex/Corpus ); précédent : 000843; suivant : 000845A study of PAF‐induced ocular inflammation in the rat and its inhibition by the PAF antagonist, L‐652, 731
Auteurs : P. D. Gautheron ; L. Coulbault ; M. F. SugrueSource :
- Journal of Pharmacy and Pharmacology [ 0022-3573 ] ; 1987-10.
English descriptors
- Teeft :
- Agents actions, Bisdesethylchloroquine, Chloroquine, Conjunctiva, Conjunctival, Conjunctival inflammation, Desethylchloroquine, Dohme research laboratories, Dos, Excretion, Goldenberg meurer, Indomethacin, Inflammation, Inflammatory, Inflammatory response, Oral administration, Parent compound, Pharm, Pharmacol, Pretreatment, Receptor, Receptor antagonist, Significant blockade, Significant reduction, Subconjunctival, Subconjunctival injection, Subconjunctivally, Tissue distribution, Tissue weight, Topical administration, Upper conjunctiva, Urinary excretion.
Abstract
A significant inflammatory reaction in the rat conjunctiva followed the subconjunctival injection of synthetic platelet activating factor (PAF) in doses which ranged from 10 ng to 1 μg, an inflammatory response being evaluated as the increase in both tissue weight and extravasation of Evans blue dye in the conjunctival tissue. Inflammation was still present 6 h after the injection of 0ṁ1 μg of PAF. Orally administered indomethacin or BW 755C failed to alter the response to 0ṁ1 μg of PAF. In contrast, the PAF‐induced inflammation was blocked by the oral administration of the PAF receptor antagonist, L‐652, 731, a dose as low as 5 mg kg−1 eliciting a significant inhibition. The topical administration of L‐652, 731, (two doses of 100 μg as a 1% suspension), elicited a slight, but significant blockade of 23%. Its antagonistic action was more striking when it was co‐injected subconjunctivally with 0ṁ1 μg of PAF, a dose as low as 3 μg evoking a significant blockade. The topical administration of 0ṁ1 μg of PAF did not elicit a significant inflammatory reaction and this contrasts with the results obtained after its subconjunctival injection.
Url:
DOI: 10.1111/j.2042-7158.1987.tb05135.x
Links to Exploration step
ISTEX:3C2AD7F7EDBD901EDF74DA14ED8D9F0C8B397BECLe document en format XML
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Gautheron</name><affiliation><mods:affiliation>Centre de Recherche, Merck Sharp & Dohme‐Chibret, 63203 Riom‐Cedex, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: Centre de Recherche, Merck Sharp & Dohme‐Chibret, 63203 Riom‐Cedex, France</mods:affiliation></affiliation></author><author><name sortKey="Coulbault, L" sort="Coulbault, L" uniqKey="Coulbault L" first="L." last="Coulbault">L. Coulbault</name><affiliation><mods:affiliation>Centre de Recherche, Merck Sharp & Dohme‐Chibret, 63203 Riom‐Cedex, France</mods:affiliation></affiliation></author><author><name sortKey="Sugrue, M F" sort="Sugrue, M F" uniqKey="Sugrue M" first="M. F." last="Sugrue">M. F. Sugrue</name><affiliation><mods:affiliation>Centre de Recherche, Merck Sharp & Dohme‐Chibret, 63203 Riom‐Cedex, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Pharmacy and Pharmacology</title><title level="j" type="alt">JOURNAL OF PHARMACY AND PHARMACOLOGY</title><idno type="ISSN">0022-3573</idno><idno type="eISSN">2042-7158</idno><imprint><biblScope unit="vol">39</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="857">857</biblScope><biblScope unit="page" to="859">859</biblScope><biblScope unit="page-count">3</biblScope><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="1987-10">1987-10</date></imprint><idno type="ISSN">0022-3573</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3573</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Agents actions</term><term>Bisdesethylchloroquine</term><term>Chloroquine</term><term>Conjunctiva</term><term>Conjunctival</term><term>Conjunctival inflammation</term><term>Desethylchloroquine</term><term>Dohme research laboratories</term><term>Dos</term><term>Excretion</term><term>Goldenberg meurer</term><term>Indomethacin</term><term>Inflammation</term><term>Inflammatory</term><term>Inflammatory response</term><term>Oral administration</term><term>Parent compound</term><term>Pharm</term><term>Pharmacol</term><term>Pretreatment</term><term>Receptor</term><term>Receptor antagonist</term><term>Significant blockade</term><term>Significant reduction</term><term>Subconjunctival</term><term>Subconjunctival injection</term><term>Subconjunctivally</term><term>Tissue distribution</term><term>Tissue weight</term><term>Topical administration</term><term>Upper conjunctiva</term><term>Urinary excretion</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A significant inflammatory reaction in the rat conjunctiva followed the subconjunctival injection of synthetic platelet activating factor (PAF) in doses which ranged from 10 ng to 1 μg, an inflammatory response being evaluated as the increase in both tissue weight and extravasation of Evans blue dye in the conjunctival tissue. Inflammation was still present 6 h after the injection of 0ṁ1 μg of PAF. Orally administered indomethacin or BW 755C failed to alter the response to 0ṁ1 μg of PAF. In contrast, the PAF‐induced inflammation was blocked by the oral administration of the PAF receptor antagonist, L‐652, 731, a dose as low as 5 mg kg−1 eliciting a significant inhibition. The topical administration of L‐652, 731, (two doses of 100 μg as a 1% suspension), elicited a slight, but significant blockade of 23%. Its antagonistic action was more striking when it was co‐injected subconjunctivally with 0ṁ1 μg of PAF, a dose as low as 3 μg evoking a significant blockade. 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D.</forename><surname>Gautheron</surname></persName><affiliation><orgName type="division">Centre de Recherche</orgName><address><addrLine>Merck Sharp & Dohme‐Chibret</addrLine><addrLine>63203 Riom‐Cedex, France</addrLine><country key="FR" xml:lang="en">FRANCE</country></address></affiliation></author><author xml:id="author-0001"><persName><forename type="first">L.</forename><surname>Coulbault</surname></persName><affiliation><orgName type="division">Centre de Recherche</orgName><address><addrLine>Merck Sharp & Dohme‐Chibret</addrLine><addrLine>63203 Riom‐Cedex, France</addrLine><country key="FR" xml:lang="en">FRANCE</country></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">M. 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The topical administration of 0ṁ1 μg of PAF did not elicit a significant inflammatory reaction and this contrasts with the results obtained after its subconjunctival injection.</p></abstract><textClass><keywords rend="tocHeading1"><term>Communications</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc><revisionDesc><change when="2019-12-20" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-XV9K141B-T/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Publishing Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)2042-7158</doi><issn type="print">0022-3573</issn><issn type="electronic">2042-7158</issn><idGroup><id type="product" value="JPHP"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="JOURNAL OF PHARMACY AND PHARMACOLOGY">Journal of Pharmacy and Pharmacology</title></titleGroup></publicationMeta><publicationMeta level="part" position="10110"><doi origin="wiley">10.1111/jphp.1987.39.issue-10</doi><numberingGroup><numbering type="journalVolume" number="39">39</numbering><numbering type="journalIssue" number="10">10</numbering></numberingGroup><coverDate startDate="1987-10">October 1987</coverDate></publicationMeta><publicationMeta level="unit" type="miscellaneous" position="19" status="forIssue"><doi origin="wiley">10.1111/j.2042-7158.1987.tb05135.x</doi><idGroup><id type="unit" value="JPHP5135"></id></idGroup><countGroup><count type="pageTotal" number="3"></count></countGroup><titleGroup><title type="tocHeading1">Communications</title></titleGroup><copyright>1987 Royal Pharmaceutical Society of Great Britain</copyright><eventGroup><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.4.7 mode:FullText" date="2011-03-11"></event><event type="firstOnline" date="2011-04-12"></event><event type="publishedOnlineFinalForm" date="2011-04-12"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-01"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-30"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="857">857</numbering><numbering type="pageLast" number="859">859</numbering></numberingGroup><correspondenceTo>Centre de Recherche, Merck Sharp & Dohme‐Chibret, 63203 Riom‐Cedex, France</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:JPHP.JPHP5135.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Communicated May 26, 1987</unparsedEditorialHistory><countGroup><count type="referenceTotal" number="17"></count><count type="linksCrossRef" number="5"></count></countGroup><titleGroup><title type="main">A study of PAF‐induced ocular inflammation in the rat and its inhibition by the PAF antagonist, L‐652, 731</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1" corresponding="yes"><personName><givenNames>P. D.</givenNames><familyName>Gautheron</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>L.</givenNames><familyName>Coulbault</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1" noteRef="#fn1"><personName><givenNames>M. F.</givenNames><familyName>Sugrue</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="FR"><unparsedAffiliation>Centre de Recherche, Merck Sharp & Dohme‐Chibret, 63203 Riom‐Cedex, France</unparsedAffiliation></affiliation></affiliationGroup><abstractGroup><abstract type="main" xml:lang="en"><p>A significant inflammatory reaction in the rat conjunctiva followed the subconjunctival injection of synthetic platelet activating factor (PAF) in doses which ranged from 10 ng to 1 μg, an inflammatory response being evaluated as the increase in both tissue weight and extravasation of Evans blue dye in the conjunctival tissue. Inflammation was still present 6 h after the injection of 0ṁ1 μg of PAF. Orally administered indomethacin or BW 755C failed to alter the response to 0ṁ1 μg of PAF. In contrast, the PAF‐induced inflammation was blocked by the oral administration of the PAF receptor antagonist, L‐652, 731, a dose as low as 5 mg kg<sup>−1</sup> eliciting a significant inhibition. The topical administration of L‐652, 731, (two doses of 100 μg as a 1% suspension), elicited a slight, but significant blockade of 23%. Its antagonistic action was more striking when it was co‐injected subconjunctivally with 0ṁ1 μg of PAF, a dose as low as 3 μg evoking a significant blockade. The topical administration of 0ṁ1 μg of PAF did not elicit a significant inflammatory reaction and this contrasts with the results obtained after its subconjunctival injection.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Merck Sharp & Dohme Research Laboratories, WP 26‐208, West Point, PA 19486, USA</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>A study of PAF‐induced ocular inflammation in the rat and its inhibition by the PAF antagonist, L‐652, 731</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>A study of PAF‐induced ocular inflammation in the rat and its inhibition by the PAF antagonist, L‐652, 731</title></titleInfo><name type="personal"><namePart type="given">P. D.</namePart><namePart type="family">Gautheron</namePart><affiliation>Centre de Recherche, Merck Sharp & Dohme‐Chibret, 63203 Riom‐Cedex, France</affiliation><affiliation>Correspondence address: Centre de Recherche, Merck Sharp & Dohme‐Chibret, 63203 Riom‐Cedex, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L.</namePart><namePart type="family">Coulbault</namePart><affiliation>Centre de Recherche, Merck Sharp & Dohme‐Chibret, 63203 Riom‐Cedex, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M. F.</namePart><namePart type="family">Sugrue</namePart><affiliation>Centre de Recherche, Merck Sharp & Dohme‐Chibret, 63203 Riom‐Cedex, France</affiliation><description>Merck Sharp & Dohme Research Laboratories, WP 26‐208, West Point, PA 19486, USA</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="miscellaneous" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">1987-10</dateIssued><edition>Communicated May 26, 1987</edition><copyrightDate encoding="w3cdtf">1987</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="references">17</extent><extent unit="linksCrossRef">5</extent></physicalDescription><abstract lang="en">A significant inflammatory reaction in the rat conjunctiva followed the subconjunctival injection of synthetic platelet activating factor (PAF) in doses which ranged from 10 ng to 1 μg, an inflammatory response being evaluated as the increase in both tissue weight and extravasation of Evans blue dye in the conjunctival tissue. Inflammation was still present 6 h after the injection of 0ṁ1 μg of PAF. Orally administered indomethacin or BW 755C failed to alter the response to 0ṁ1 μg of PAF. In contrast, the PAF‐induced inflammation was blocked by the oral administration of the PAF receptor antagonist, L‐652, 731, a dose as low as 5 mg kg−1 eliciting a significant inhibition. The topical administration of L‐652, 731, (two doses of 100 μg as a 1% suspension), elicited a slight, but significant blockade of 23%. Its antagonistic action was more striking when it was co‐injected subconjunctivally with 0ṁ1 μg of PAF, a dose as low as 3 μg evoking a significant blockade. 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