Comparative analysis of isolated human bronchi contraction and biosynthesis of cysteinyl leukotrienes using a direct 5-lipoxygenase inhibitor
Quantitation of cysteinyl leukotriene production and smooth muscle contraction upon immunological challenge of isolated human bronchi was evaluated. Analysis of picomole amounts of leukotriene C 4, D 4, and E 4 was achieved using HPLC separation and enzyme immunoassay quantitative determination. The...
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Veröffentlicht in: | Biochemical pharmacology 1997-08, Vol.54 (4), p.437-442 |
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creator | Bolla, Manlio Caruso, Paola Giossi, Massimo Folco, Giancarlo Civelli, Maurizio Sala, Angelo |
description | Quantitation of cysteinyl leukotriene production and smooth muscle contraction upon immunological challenge of isolated human bronchi was evaluated. Analysis of picomole amounts of leukotriene C
4, D
4, and E
4 was achieved using HPLC separation and enzyme immunoassay quantitative determination. The aim of the study was to correlate the contraction of airway smooth muscle and cysteinyl leukotriene production with and without 5-lipoxygenase inhibition. In human isolated bronchial tissue treated with indomethacin and pyrilamine to make their contractile responses leukotriene dependent only, the novel 5-lipoxygenase inhibitor 5,6-Dihydroxy-2-(
N,
N-Dimethylhydrazino)-1,2,3,4-tetrahydro-naphtalene bromide (CHF 1909) caused a concentration-dependent inhibition of the immunologically induced contraction, showing an IC
50 value of 13 ± 2.2 μM (mean ± CV). At the concentration of 30 (μM, this compound caused more than 90% inhibition of the maximal bronchoconstriction
in vitro, and inhibited cysteinyl leukotriene production by 90% as well. Contemporary measurement of immunologically induced contraction and production of cysteinyl leukotrienes in isolated human bronchi provided a direct correlation between smooth muscle contraction and synthesis of leukotriene C
4, D
4, and E
4. |
doi_str_mv | 10.1016/S0006-2952(97)00055-5 |
format | Article |
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4, D
4, and E
4 was achieved using HPLC separation and enzyme immunoassay quantitative determination. The aim of the study was to correlate the contraction of airway smooth muscle and cysteinyl leukotriene production with and without 5-lipoxygenase inhibition. In human isolated bronchial tissue treated with indomethacin and pyrilamine to make their contractile responses leukotriene dependent only, the novel 5-lipoxygenase inhibitor 5,6-Dihydroxy-2-(
N,
N-Dimethylhydrazino)-1,2,3,4-tetrahydro-naphtalene bromide (CHF 1909) caused a concentration-dependent inhibition of the immunologically induced contraction, showing an IC
50 value of 13 ± 2.2 μM (mean ± CV). At the concentration of 30 (μM, this compound caused more than 90% inhibition of the maximal bronchoconstriction
in vitro, and inhibited cysteinyl leukotriene production by 90% as well. Contemporary measurement of immunologically induced contraction and production of cysteinyl leukotrienes in isolated human bronchi provided a direct correlation between smooth muscle contraction and synthesis of leukotriene C
4, D
4, and E
4.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/S0006-2952(97)00055-5</identifier><identifier>PMID: 9313769</identifier><identifier>CODEN: BCPCA6</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>5-lipoxygenase inhibition ; Biological and medical sciences ; Bronchi - metabolism ; Bronchoconstriction - drug effects ; Cysteine - biosynthesis ; cysteinyl leukotrienes ; Dose-Response Relationship, Drug ; HPLC, enzyme immunoassay ; Humans ; Immunoglobulin E - immunology ; immunological challenge ; In Vitro Techniques ; isolated human bronchi ; Leukotrienes - biosynthesis ; Lipoxygenase Inhibitors - pharmacology ; Medical sciences ; Pharmacology. Drug treatments ; Respiratory system</subject><ispartof>Biochemical pharmacology, 1997-08, Vol.54 (4), p.437-442</ispartof><rights>1997</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-515a67a3412247097eb7d5ae492d840e307c3f7ac70adada4ec04cc7efcb09d73</citedby><cites>FETCH-LOGICAL-c455t-515a67a3412247097eb7d5ae492d840e307c3f7ac70adada4ec04cc7efcb09d73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-2952(97)00055-5$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2811897$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9313769$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bolla, Manlio</creatorcontrib><creatorcontrib>Caruso, Paola</creatorcontrib><creatorcontrib>Giossi, Massimo</creatorcontrib><creatorcontrib>Folco, Giancarlo</creatorcontrib><creatorcontrib>Civelli, Maurizio</creatorcontrib><creatorcontrib>Sala, Angelo</creatorcontrib><title>Comparative analysis of isolated human bronchi contraction and biosynthesis of cysteinyl leukotrienes using a direct 5-lipoxygenase inhibitor</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>Quantitation of cysteinyl leukotriene production and smooth muscle contraction upon immunological challenge of isolated human bronchi was evaluated. Analysis of picomole amounts of leukotriene C
4, D
4, and E
4 was achieved using HPLC separation and enzyme immunoassay quantitative determination. The aim of the study was to correlate the contraction of airway smooth muscle and cysteinyl leukotriene production with and without 5-lipoxygenase inhibition. In human isolated bronchial tissue treated with indomethacin and pyrilamine to make their contractile responses leukotriene dependent only, the novel 5-lipoxygenase inhibitor 5,6-Dihydroxy-2-(
N,
N-Dimethylhydrazino)-1,2,3,4-tetrahydro-naphtalene bromide (CHF 1909) caused a concentration-dependent inhibition of the immunologically induced contraction, showing an IC
50 value of 13 ± 2.2 μM (mean ± CV). At the concentration of 30 (μM, this compound caused more than 90% inhibition of the maximal bronchoconstriction
in vitro, and inhibited cysteinyl leukotriene production by 90% as well. Contemporary measurement of immunologically induced contraction and production of cysteinyl leukotrienes in isolated human bronchi provided a direct correlation between smooth muscle contraction and synthesis of leukotriene C
4, D
4, and E
4.</description><subject>5-lipoxygenase inhibition</subject><subject>Biological and medical sciences</subject><subject>Bronchi - metabolism</subject><subject>Bronchoconstriction - drug effects</subject><subject>Cysteine - biosynthesis</subject><subject>cysteinyl leukotrienes</subject><subject>Dose-Response Relationship, Drug</subject><subject>HPLC, enzyme immunoassay</subject><subject>Humans</subject><subject>Immunoglobulin E - immunology</subject><subject>immunological challenge</subject><subject>In Vitro Techniques</subject><subject>isolated human bronchi</subject><subject>Leukotrienes - biosynthesis</subject><subject>Lipoxygenase Inhibitors - pharmacology</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Respiratory system</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQxi0EKtvCI1TyASF6CNhJHCcnVK34J1XiAJytiTPpDmTtxXYq8hC8M95utFfkgzWe3zcefR9j11K8lUI2774JIZqi7FT5ptM3uVCqUE_YRra6ys9N-5Rtzshzdhnjz2PZNvKCXXSVrHTTbdjfrd8fIECiB-TgYFoiRe5HTtFPkHDgu3kPjvfBO7sjbr1LAWwi7zI-8J58XFza4SqzS0xIbpn4hPMvnwKhw8jnSO6eAx8ooE1cFRMd_J_lHh1E5OR21FPy4QV7NsIU8eV6X7EfHz98334u7r5--rK9vStsrVQqlFTQaKhqWZa1Fp3GXg8KsO7Koa0FVkLbatRgtYAhnxqtqK3VONpedIOurtjr09xD8L9njMnsKVqcJnDo52h09qfWjcygOoE2-BgDjuYQaA9hMVKYYwzmMQZz9Nh02jzGYFTWXa8fzP0eh7Nq9T33X619iBamMYCzFM9Y2UrZdsc9358wzGY8EAYTbTbU4slHM3j6zyL_AD7tqHA</recordid><startdate>19970815</startdate><enddate>19970815</enddate><creator>Bolla, Manlio</creator><creator>Caruso, Paola</creator><creator>Giossi, Massimo</creator><creator>Folco, Giancarlo</creator><creator>Civelli, Maurizio</creator><creator>Sala, Angelo</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19970815</creationdate><title>Comparative analysis of isolated human bronchi contraction and biosynthesis of cysteinyl leukotrienes using a direct 5-lipoxygenase inhibitor</title><author>Bolla, Manlio ; Caruso, Paola ; Giossi, Massimo ; Folco, Giancarlo ; Civelli, Maurizio ; Sala, Angelo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-515a67a3412247097eb7d5ae492d840e307c3f7ac70adada4ec04cc7efcb09d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>5-lipoxygenase inhibition</topic><topic>Biological and medical sciences</topic><topic>Bronchi - metabolism</topic><topic>Bronchoconstriction - drug effects</topic><topic>Cysteine - biosynthesis</topic><topic>cysteinyl leukotrienes</topic><topic>Dose-Response Relationship, Drug</topic><topic>HPLC, enzyme immunoassay</topic><topic>Humans</topic><topic>Immunoglobulin E - immunology</topic><topic>immunological challenge</topic><topic>In Vitro Techniques</topic><topic>isolated human bronchi</topic><topic>Leukotrienes - biosynthesis</topic><topic>Lipoxygenase Inhibitors - pharmacology</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Respiratory system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bolla, Manlio</creatorcontrib><creatorcontrib>Caruso, Paola</creatorcontrib><creatorcontrib>Giossi, Massimo</creatorcontrib><creatorcontrib>Folco, Giancarlo</creatorcontrib><creatorcontrib>Civelli, Maurizio</creatorcontrib><creatorcontrib>Sala, Angelo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bolla, Manlio</au><au>Caruso, Paola</au><au>Giossi, Massimo</au><au>Folco, Giancarlo</au><au>Civelli, Maurizio</au><au>Sala, Angelo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative analysis of isolated human bronchi contraction and biosynthesis of cysteinyl leukotrienes using a direct 5-lipoxygenase inhibitor</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>1997-08-15</date><risdate>1997</risdate><volume>54</volume><issue>4</issue><spage>437</spage><epage>442</epage><pages>437-442</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><coden>BCPCA6</coden><abstract>Quantitation of cysteinyl leukotriene production and smooth muscle contraction upon immunological challenge of isolated human bronchi was evaluated. Analysis of picomole amounts of leukotriene C
4, D
4, and E
4 was achieved using HPLC separation and enzyme immunoassay quantitative determination. The aim of the study was to correlate the contraction of airway smooth muscle and cysteinyl leukotriene production with and without 5-lipoxygenase inhibition. In human isolated bronchial tissue treated with indomethacin and pyrilamine to make their contractile responses leukotriene dependent only, the novel 5-lipoxygenase inhibitor 5,6-Dihydroxy-2-(
N,
N-Dimethylhydrazino)-1,2,3,4-tetrahydro-naphtalene bromide (CHF 1909) caused a concentration-dependent inhibition of the immunologically induced contraction, showing an IC
50 value of 13 ± 2.2 μM (mean ± CV). At the concentration of 30 (μM, this compound caused more than 90% inhibition of the maximal bronchoconstriction
in vitro, and inhibited cysteinyl leukotriene production by 90% as well. Contemporary measurement of immunologically induced contraction and production of cysteinyl leukotrienes in isolated human bronchi provided a direct correlation between smooth muscle contraction and synthesis of leukotriene C
4, D
4, and E
4.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>9313769</pmid><doi>10.1016/S0006-2952(97)00055-5</doi><tpages>6</tpages></addata></record> |
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subjects | 5-lipoxygenase inhibition Biological and medical sciences Bronchi - metabolism Bronchoconstriction - drug effects Cysteine - biosynthesis cysteinyl leukotrienes Dose-Response Relationship, Drug HPLC, enzyme immunoassay Humans Immunoglobulin E - immunology immunological challenge In Vitro Techniques isolated human bronchi Leukotrienes - biosynthesis Lipoxygenase Inhibitors - pharmacology Medical sciences Pharmacology. Drug treatments Respiratory system |
title | Comparative analysis of isolated human bronchi contraction and biosynthesis of cysteinyl leukotrienes using a direct 5-lipoxygenase inhibitor |
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