Pharmacological Modulation of Antigen-Induced Airway Hyperresponsiveness by Thromboxane A2 Inhibitors in Guinea Pigs
The effects of OKY-046 (thromboxane A2 (TXA2) synthetase inhibitor) and ONO-3708 (TXA2 receptor antagonist) on antigen-induced airway hyperreactivity in guinea pigs were investigated. Ketotifen was used as a reference drug. Seven inhalations of an antigen into actively sensitized animals resulted in...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 1993/11/15, Vol.16(11), pp.1099-1103 |
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| creator | NAGAI, Hiroichi TSUJI, Fumio GOTO, Shouichi KODA, Akihide |
| description | The effects of OKY-046 (thromboxane A2 (TXA2) synthetase inhibitor) and ONO-3708 (TXA2 receptor antagonist) on antigen-induced airway hyperreactivity in guinea pigs were investigated. Ketotifen was used as a reference drug. Seven inhalations of an antigen into actively sensitized animals resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (macrophages, neutrophils, eosinophils and lymphocytes) and the quantity of mediators (thromboxane B2, leukotriene D4 and histamine) in bronchoalveolar lavage fluid increased.All examined drugs inhibited the antigen-induced airway hyperreactivity to acetylcholine. Whereas ketotifen inhibited an accumulation of inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid, OKY-046 and ONO-3708 had no effect on the accumulation of inflammatory cells. OKY-046, but not ketotifen and ONO-3708, inhibited an increase of thromboxane B2 in the bronchoalveolar lavage fluid after antigen provocation.These results suggest the participation of TXA2 in the onset of antigen-induced airway hyperresponsiveness in guinea pigs, and the efficacy of TXA2 inhibitors, without affecting the accumulation of inflammatory cells in bronchoalveolar lavage fluid. |
| doi_str_mv | 10.1248/bpb.16.1099 |
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Ketotifen was used as a reference drug. Seven inhalations of an antigen into actively sensitized animals resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (macrophages, neutrophils, eosinophils and lymphocytes) and the quantity of mediators (thromboxane B2, leukotriene D4 and histamine) in bronchoalveolar lavage fluid increased.All examined drugs inhibited the antigen-induced airway hyperreactivity to acetylcholine. Whereas ketotifen inhibited an accumulation of inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid, OKY-046 and ONO-3708 had no effect on the accumulation of inflammatory cells. OKY-046, but not ketotifen and ONO-3708, inhibited an increase of thromboxane B2 in the bronchoalveolar lavage fluid after antigen provocation.These results suggest the participation of TXA2 in the onset of antigen-induced airway hyperresponsiveness in guinea pigs, and the efficacy of TXA2 inhibitors, without affecting the accumulation of inflammatory cells in bronchoalveolar lavage fluid.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.16.1099</identifier><identifier>PMID: 8312863</identifier><language>eng</language><publisher>Tokyo: The Pharmaceutical Society of Japan</publisher><subject>Acetylcholine ; Administration, Inhalation ; airway hyperreactivity ; airway inflammation ; Animals ; Biological and medical sciences ; Bronchi - drug effects ; Bronchi - pathology ; Bronchial Hyperreactivity - drug therapy ; Bronchial Hyperreactivity - pathology ; Bronchial Hyperreactivity - physiopathology ; Bronchoalveolar Lavage Fluid - chemistry ; Bronchoalveolar Lavage Fluid - cytology ; Guinea Pigs ; Histamine and antagonists. Allergy ; Ketotifen - pharmacology ; Leukocyte Count - drug effects ; Male ; Medical sciences ; Methacrylates - administration & dosage ; Methacrylates - pharmacology ; OKY-046 ; ONO-3708 ; Pharmacology. Drug treatments ; thromboxane A2 ; Thromboxane A2 - administration & dosage ; Thromboxane A2 - analogs & derivatives ; Thromboxane A2 - antagonists & inhibitors ; Thromboxane A2 - pharmacology ; Thromboxane A2 - physiology ; Thromboxane-A Synthase - antagonists & inhibitors ; Trachea - drug effects ; Trachea - pathology</subject><ispartof>Biological and Pharmaceutical Bulletin, 1993/11/15, Vol.16(11), pp.1099-1103</ispartof><rights>The Pharmaceutical Society of Japan</rights><rights>1994 INIST-CNRS</rights><rights>Copyright Japan Science and Technology Agency 1993</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5239-ebad8c56bb609c6f338d44509b32fac33dc2e9effd1cf2d921eb9cd700e41d3e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3988361$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8312863$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>NAGAI, Hiroichi</creatorcontrib><creatorcontrib>TSUJI, Fumio</creatorcontrib><creatorcontrib>GOTO, Shouichi</creatorcontrib><creatorcontrib>KODA, Akihide</creatorcontrib><title>Pharmacological Modulation of Antigen-Induced Airway Hyperresponsiveness by Thromboxane A2 Inhibitors in Guinea Pigs</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>The effects of OKY-046 (thromboxane A2 (TXA2) synthetase inhibitor) and ONO-3708 (TXA2 receptor antagonist) on antigen-induced airway hyperreactivity in guinea pigs were investigated. Ketotifen was used as a reference drug. Seven inhalations of an antigen into actively sensitized animals resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (macrophages, neutrophils, eosinophils and lymphocytes) and the quantity of mediators (thromboxane B2, leukotriene D4 and histamine) in bronchoalveolar lavage fluid increased.All examined drugs inhibited the antigen-induced airway hyperreactivity to acetylcholine. Whereas ketotifen inhibited an accumulation of inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid, OKY-046 and ONO-3708 had no effect on the accumulation of inflammatory cells. OKY-046, but not ketotifen and ONO-3708, inhibited an increase of thromboxane B2 in the bronchoalveolar lavage fluid after antigen provocation.These results suggest the participation of TXA2 in the onset of antigen-induced airway hyperresponsiveness in guinea pigs, and the efficacy of TXA2 inhibitors, without affecting the accumulation of inflammatory cells in bronchoalveolar lavage fluid.</description><subject>Acetylcholine</subject><subject>Administration, Inhalation</subject><subject>airway hyperreactivity</subject><subject>airway inflammation</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bronchi - drug effects</subject><subject>Bronchi - pathology</subject><subject>Bronchial Hyperreactivity - drug therapy</subject><subject>Bronchial Hyperreactivity - pathology</subject><subject>Bronchial Hyperreactivity - physiopathology</subject><subject>Bronchoalveolar Lavage Fluid - chemistry</subject><subject>Bronchoalveolar Lavage Fluid - cytology</subject><subject>Guinea Pigs</subject><subject>Histamine and antagonists. Allergy</subject><subject>Ketotifen - pharmacology</subject><subject>Leukocyte Count - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Methacrylates - administration & dosage</subject><subject>Methacrylates - pharmacology</subject><subject>OKY-046</subject><subject>ONO-3708</subject><subject>Pharmacology. Drug treatments</subject><subject>thromboxane A2</subject><subject>Thromboxane A2 - administration & dosage</subject><subject>Thromboxane A2 - analogs & derivatives</subject><subject>Thromboxane A2 - antagonists & inhibitors</subject><subject>Thromboxane A2 - pharmacology</subject><subject>Thromboxane A2 - physiology</subject><subject>Thromboxane-A Synthase - antagonists & inhibitors</subject><subject>Trachea - drug effects</subject><subject>Trachea - pathology</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUuP0zAURi0EGsrAijWSJRAblOJH4sTLasTMVBrELIa15cdN6yqxi50A_fe4tHTBxl58R_dc3Q-ht5QsKau7z2ZvllQsKZHyGVpQXrdVw2jzHC2IpF0laNO9RK9y3hFCWsL4FbrqOGWd4As0PW51GrWNQ9x4qwf8Nbp50JOPAccer8LkNxCqdXCzBYdXPv3SB3x_2ENKkPcxZP8TAuSMzQE_bVMcTfytA-AVw-uw9cZPMWXsA76bfQCNH_0mv0Yvej1keHP-r9H32y9PN_fVw7e79c3qobIN47ICo11nG2GMINKKnvPO1XVDpOGs15ZzZxlI6HtHbc-cZBSMtK4lBGrqOPBr9PE0d5_ijxnypEafLQxDWTDOWbWCMc66toDv_wN3cU6h7KZoXUvaCElooT6dKJtizgl6tU9-1OmgKFHHJlRpQlGhjk0U-t155mxGcBf2fPqSfzjnOpfD90kH6_MF47LruDhKb0_YLk96A5dcp8nbAY5KWmx_tfTfW_wXwJaCFQT-ByA-qrU</recordid><startdate>1993</startdate><enddate>1993</enddate><creator>NAGAI, Hiroichi</creator><creator>TSUJI, Fumio</creator><creator>GOTO, Shouichi</creator><creator>KODA, Akihide</creator><general>The Pharmaceutical Society of Japan</general><general>Maruzen</general><general>Japan Science and Technology Agency</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>1993</creationdate><title>Pharmacological Modulation of Antigen-Induced Airway Hyperresponsiveness by Thromboxane A2 Inhibitors in Guinea Pigs</title><author>NAGAI, Hiroichi ; TSUJI, Fumio ; GOTO, Shouichi ; KODA, Akihide</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5239-ebad8c56bb609c6f338d44509b32fac33dc2e9effd1cf2d921eb9cd700e41d3e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Acetylcholine</topic><topic>Administration, Inhalation</topic><topic>airway hyperreactivity</topic><topic>airway inflammation</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bronchi - drug effects</topic><topic>Bronchi - pathology</topic><topic>Bronchial Hyperreactivity - drug therapy</topic><topic>Bronchial Hyperreactivity - pathology</topic><topic>Bronchial Hyperreactivity - physiopathology</topic><topic>Bronchoalveolar Lavage Fluid - chemistry</topic><topic>Bronchoalveolar Lavage Fluid - cytology</topic><topic>Guinea Pigs</topic><topic>Histamine and antagonists. Allergy</topic><topic>Ketotifen - pharmacology</topic><topic>Leukocyte Count - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methacrylates - administration & dosage</topic><topic>Methacrylates - pharmacology</topic><topic>OKY-046</topic><topic>ONO-3708</topic><topic>Pharmacology. Drug treatments</topic><topic>thromboxane A2</topic><topic>Thromboxane A2 - administration & dosage</topic><topic>Thromboxane A2 - analogs & derivatives</topic><topic>Thromboxane A2 - antagonists & inhibitors</topic><topic>Thromboxane A2 - pharmacology</topic><topic>Thromboxane A2 - physiology</topic><topic>Thromboxane-A Synthase - antagonists & inhibitors</topic><topic>Trachea - drug effects</topic><topic>Trachea - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>NAGAI, Hiroichi</creatorcontrib><creatorcontrib>TSUJI, Fumio</creatorcontrib><creatorcontrib>GOTO, Shouichi</creatorcontrib><creatorcontrib>KODA, Akihide</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>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>NAGAI, Hiroichi</au><au>TSUJI, Fumio</au><au>GOTO, Shouichi</au><au>KODA, Akihide</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacological Modulation of Antigen-Induced Airway Hyperresponsiveness by Thromboxane A2 Inhibitors in Guinea Pigs</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>1993</date><risdate>1993</risdate><volume>16</volume><issue>11</issue><spage>1099</spage><epage>1103</epage><pages>1099-1103</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>The effects of OKY-046 (thromboxane A2 (TXA2) synthetase inhibitor) and ONO-3708 (TXA2 receptor antagonist) on antigen-induced airway hyperreactivity in guinea pigs were investigated. Ketotifen was used as a reference drug. Seven inhalations of an antigen into actively sensitized animals resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (macrophages, neutrophils, eosinophils and lymphocytes) and the quantity of mediators (thromboxane B2, leukotriene D4 and histamine) in bronchoalveolar lavage fluid increased.All examined drugs inhibited the antigen-induced airway hyperreactivity to acetylcholine. Whereas ketotifen inhibited an accumulation of inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid, OKY-046 and ONO-3708 had no effect on the accumulation of inflammatory cells. OKY-046, but not ketotifen and ONO-3708, inhibited an increase of thromboxane B2 in the bronchoalveolar lavage fluid after antigen provocation.These results suggest the participation of TXA2 in the onset of antigen-induced airway hyperresponsiveness in guinea pigs, and the efficacy of TXA2 inhibitors, without affecting the accumulation of inflammatory cells in bronchoalveolar lavage fluid.</abstract><cop>Tokyo</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>8312863</pmid><doi>10.1248/bpb.16.1099</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylcholine Administration, Inhalation airway hyperreactivity airway inflammation Animals Biological and medical sciences Bronchi - drug effects Bronchi - pathology Bronchial Hyperreactivity - drug therapy Bronchial Hyperreactivity - pathology Bronchial Hyperreactivity - physiopathology Bronchoalveolar Lavage Fluid - chemistry Bronchoalveolar Lavage Fluid - cytology Guinea Pigs Histamine and antagonists. Allergy Ketotifen - pharmacology Leukocyte Count - drug effects Male Medical sciences Methacrylates - administration & dosage Methacrylates - pharmacology OKY-046 ONO-3708 Pharmacology. Drug treatments thromboxane A2 Thromboxane A2 - administration & dosage Thromboxane A2 - analogs & derivatives Thromboxane A2 - antagonists & inhibitors Thromboxane A2 - pharmacology Thromboxane A2 - physiology Thromboxane-A Synthase - antagonists & inhibitors Trachea - drug effects Trachea - pathology |
| title | Pharmacological Modulation of Antigen-Induced Airway Hyperresponsiveness by Thromboxane A2 Inhibitors in Guinea Pigs |
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