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Article: Partial agonist effect of the platelet-activating factor receptor antagonists, WEB 2086 and WEB 2170, in the rat perfused heart

TitlePartial agonist effect of the platelet-activating factor receptor antagonists, WEB 2086 and WEB 2170, in the rat perfused heart
Authors
Issue Date1993
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 1993, v. 110 n. 2, p. 645-650 How to Cite?
Abstract1. WEB 2086 and WEB 2170 are potent platelet-activating factor (PAF) receptor antagonists and have been used widely as pharmacological tools to investigate the actions of PAF in a variety of biological systems. 2. Low concentrations of WEB 2086 and WEB 2170 blocked the vasoconstrictor action of PAF in the rat perfused heart. In this study, we observed that moderate concentrations of WEB 2086 and WEB 2170 increased the perfusion pressure in rat isolated hearts under constant flow perfusion. The vasoconstrictor actions of WEB 2086 and WEB 2170 were not observed with a structurally different PAF receptor antagonist, FR-900452. 3. To determine whether this vasoconstrictor action of WEB 2086 involved non-specific effects or was via the activation of PAF receptors, hearts were pretreated with 100 pmol PAF or 50 μM FR-900452. These pretreatments attenuated the vasoconstrictor action of 1 μM WEB 2086, suggesting that the action of WEB 2086 may be mediated via PAF receptors. Pretreatment with the leukotriene receptor antagonist (L-649,923, 5 μM) and the leukotriene synthesis inhibitor (MK-886, 10 μM) that are known to block the vasoconstrictor action of PAF receptor activation also attenuated the vasoconstrictor action of WEB 2086. Pretreatment with PAF or MK-886 attenuated the vasoconstrictor action of 0.5 μM WEB 2170. 4. When PAF receptors were activated by PAF in the perfused heart, significant amounts of leukotriene C4 and leukotriene C4/D4/E4 were detected in the coronary effluent. However, no significant amount of these leukotrienes was detected in the coronary effluent when hearts were perfused with 1 μM WEB 2086 or 0.5 μM WEB 2170. 5. In summary, our results indicate that WEB 2086 and WEB 2170 possess partial agonist effects in the rat perfused heart where they produced vasoconstriction via the activation of PAF receptor. This action could be attenuated by PAF pretreatment or a PAF receptor antagonist. The vasoconstrictor action of WEB 2086 and WEB 2170 involved the production of leukotrienes. But unlike the vasoconstrictor action of PAF, no significant amount of leukotrienes was detected in the effluent suggesting that the vasoconstrictor action of WEB 2086 and WEB 2170 may be explained on the basis of intracellularly or locally produced leukotrienes.
Persistent Identifierhttp://hdl.handle.net/10722/171091
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHu, Wen_US
dc.contributor.authorMcnicholl, IKen_US
dc.contributor.authorChoy, PCen_US
dc.contributor.authorMan, RYKen_US
dc.date.accessioned2012-10-30T06:12:09Z-
dc.date.available2012-10-30T06:12:09Z-
dc.date.issued1993en_US
dc.identifier.citationBritish Journal Of Pharmacology, 1993, v. 110 n. 2, p. 645-650en_US
dc.identifier.issn0007-1188en_US
dc.identifier.urihttp://hdl.handle.net/10722/171091-
dc.description.abstract1. WEB 2086 and WEB 2170 are potent platelet-activating factor (PAF) receptor antagonists and have been used widely as pharmacological tools to investigate the actions of PAF in a variety of biological systems. 2. Low concentrations of WEB 2086 and WEB 2170 blocked the vasoconstrictor action of PAF in the rat perfused heart. In this study, we observed that moderate concentrations of WEB 2086 and WEB 2170 increased the perfusion pressure in rat isolated hearts under constant flow perfusion. The vasoconstrictor actions of WEB 2086 and WEB 2170 were not observed with a structurally different PAF receptor antagonist, FR-900452. 3. To determine whether this vasoconstrictor action of WEB 2086 involved non-specific effects or was via the activation of PAF receptors, hearts were pretreated with 100 pmol PAF or 50 μM FR-900452. These pretreatments attenuated the vasoconstrictor action of 1 μM WEB 2086, suggesting that the action of WEB 2086 may be mediated via PAF receptors. Pretreatment with the leukotriene receptor antagonist (L-649,923, 5 μM) and the leukotriene synthesis inhibitor (MK-886, 10 μM) that are known to block the vasoconstrictor action of PAF receptor activation also attenuated the vasoconstrictor action of WEB 2086. Pretreatment with PAF or MK-886 attenuated the vasoconstrictor action of 0.5 μM WEB 2170. 4. When PAF receptors were activated by PAF in the perfused heart, significant amounts of leukotriene C4 and leukotriene C4/D4/E4 were detected in the coronary effluent. However, no significant amount of these leukotrienes was detected in the coronary effluent when hearts were perfused with 1 μM WEB 2086 or 0.5 μM WEB 2170. 5. In summary, our results indicate that WEB 2086 and WEB 2170 possess partial agonist effects in the rat perfused heart where they produced vasoconstriction via the activation of PAF receptor. This action could be attenuated by PAF pretreatment or a PAF receptor antagonist. The vasoconstrictor action of WEB 2086 and WEB 2170 involved the production of leukotrienes. But unlike the vasoconstrictor action of PAF, no significant amount of leukotrienes was detected in the effluent suggesting that the vasoconstrictor action of WEB 2086 and WEB 2170 may be explained on the basis of intracellularly or locally produced leukotrienes.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_US
dc.relation.ispartofBritish Journal of Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAzepines - Pharmacologyen_US
dc.subject.meshHeart - Drug Effectsen_US
dc.subject.meshLeukotrienes - Metabolismen_US
dc.subject.meshPerfusionen_US
dc.subject.meshPlatelet Activating Factor - Antagonists & Inhibitors - Pharmacologyen_US
dc.subject.meshPlatelet Membrane Glycoproteins - Antagonists & Inhibitorsen_US
dc.subject.meshRadioimmunoassayen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshReceptors, Cell Surfaceen_US
dc.subject.meshReceptors, G-Protein-Coupleden_US
dc.subject.meshTriazoles - Pharmacologyen_US
dc.subject.meshVasoconstriction - Drug Effectsen_US
dc.subject.meshVasodilation - Drug Effectsen_US
dc.titlePartial agonist effect of the platelet-activating factor receptor antagonists, WEB 2086 and WEB 2170, in the rat perfused hearten_US
dc.typeArticleen_US
dc.identifier.emailMan, RYK:rykman@hkucc.hku.hken_US
dc.identifier.authorityMan, RYK=rp00236en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1476-5381.1993.tb13860.x-
dc.identifier.pmid8242237-
dc.identifier.scopuseid_2-s2.0-0027261045en_US
dc.identifier.volume110en_US
dc.identifier.issue2en_US
dc.identifier.spage645en_US
dc.identifier.epage650en_US
dc.identifier.isiWOS:A1993LY79100021-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridHu, W=7404360099en_US
dc.identifier.scopusauthoridMcNicholl, IK=6603546700en_US
dc.identifier.scopusauthoridChoy, PC=7006633002en_US
dc.identifier.scopusauthoridMan, RYK=7004986435en_US

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