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Article: Inhibition of airway smooth muscle tone by a phorbol ester in the guinea pig trachea: Role of epithelium and receptor reserve of the contractile agent

TitleInhibition of airway smooth muscle tone by a phorbol ester in the guinea pig trachea: Role of epithelium and receptor reserve of the contractile agent
Authors
Issue Date1991
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.org
Citation
Journal Of Pharmacology And Experimental Therapeutics, 1991, v. 259 n. 1, p. 198-204 How to Cite?
AbstractBronchial hyperresponsiveness in patients with asthma may be associated with a damaged or dysfunctional epithelium. Also, changes in the activities of protein kinase C have been implicated in the pathogenesis of asthma. This study examined the role of protein kinase C in the modulation of airway smooth muscle tone and the influence of the epithelium on this function. Phorbol- 12,13-diacetate (PDA) (10-8 to 10-5 M) induced concentration- dependent and epithelium-independent relaxations of guinea pig tracheal rings. PDA (10-8 to 10-5 M) induced significantly greater relaxations of tracheal rings contracted with 5-hydroxytryptamine (10-5 M) than in tissues contracted to an equivalent degree with acetylcholine (10-6 M). In experiments using phenoxybenzamine (10-7 M and 10-5 M), the dissociation constant (K(A)) for acetylcholine was significantly greater than that for 5-hydroxytryptamine. The fraction of active receptors (q) calculated for acetylcholine was significantly smaller than that calculated for an equieffective concentration of 5-hydroxytryptamine. Relaxations to PDA in tissues contracted with acetylcholine (2 x 10-6 M) or 5-hydroxytryptamine (10-5 M) were significantly augmented by phenoxybenzamine (10-5 M and 10-7 M, respectively). PDA did not affect contractions to acetylcholine (10-8 to 10-3 M) in the presence of epithelium but caused a significant right-ward displacement of the acetylcholine concentration-contraction curve in the absence of epithelium. The concentration-contraction curves for 5-hydroxytryptamine (10-8 to 10-5 M) were significantly displaced to the right by PDA in the presence or absence of epithelium. This effect was greater in the absence of epithelium. These results demonstrate that the effect of stimulation of protein kinase C by PDA is epithelium-independent and may be influenced by the receptor reserve of the contractile agonist for its receptors.
Persistent Identifierhttp://hdl.handle.net/10722/171008
ISSN
2015 Impact Factor: 3.76
2015 SCImago Journal Rankings: 1.847
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMorrison, KJen_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:11:48Z-
dc.date.available2012-10-30T06:11:48Z-
dc.date.issued1991en_US
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 1991, v. 259 n. 1, p. 198-204en_US
dc.identifier.issn0022-3565en_US
dc.identifier.urihttp://hdl.handle.net/10722/171008-
dc.description.abstractBronchial hyperresponsiveness in patients with asthma may be associated with a damaged or dysfunctional epithelium. Also, changes in the activities of protein kinase C have been implicated in the pathogenesis of asthma. This study examined the role of protein kinase C in the modulation of airway smooth muscle tone and the influence of the epithelium on this function. Phorbol- 12,13-diacetate (PDA) (10-8 to 10-5 M) induced concentration- dependent and epithelium-independent relaxations of guinea pig tracheal rings. PDA (10-8 to 10-5 M) induced significantly greater relaxations of tracheal rings contracted with 5-hydroxytryptamine (10-5 M) than in tissues contracted to an equivalent degree with acetylcholine (10-6 M). In experiments using phenoxybenzamine (10-7 M and 10-5 M), the dissociation constant (K(A)) for acetylcholine was significantly greater than that for 5-hydroxytryptamine. The fraction of active receptors (q) calculated for acetylcholine was significantly smaller than that calculated for an equieffective concentration of 5-hydroxytryptamine. Relaxations to PDA in tissues contracted with acetylcholine (2 x 10-6 M) or 5-hydroxytryptamine (10-5 M) were significantly augmented by phenoxybenzamine (10-5 M and 10-7 M, respectively). PDA did not affect contractions to acetylcholine (10-8 to 10-3 M) in the presence of epithelium but caused a significant right-ward displacement of the acetylcholine concentration-contraction curve in the absence of epithelium. The concentration-contraction curves for 5-hydroxytryptamine (10-8 to 10-5 M) were significantly displaced to the right by PDA in the presence or absence of epithelium. This effect was greater in the absence of epithelium. These results demonstrate that the effect of stimulation of protein kinase C by PDA is epithelium-independent and may be influenced by the receptor reserve of the contractile agonist for its receptors.en_US
dc.languageengen_US
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.orgen_US
dc.relation.ispartofJournal of Pharmacology and Experimental Therapeuticsen_US
dc.subject.meshAcetylcholine - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshDrug Interactionsen_US
dc.subject.meshEpithelium - Physiologyen_US
dc.subject.meshGuinea Pigsen_US
dc.subject.meshMaleen_US
dc.subject.meshMuscle Contraction - Drug Effectsen_US
dc.subject.meshMuscle Relaxation - Drug Effectsen_US
dc.subject.meshMuscle, Smooth - Drug Effects - Enzymologyen_US
dc.subject.meshNitric Oxide - Physiologyen_US
dc.subject.meshPapaverine - Pharmacologyen_US
dc.subject.meshPhorbol Esters - Pharmacologyen_US
dc.subject.meshProtein Kinase C - Physiologyen_US
dc.subject.meshSerotonin - Pharmacologyen_US
dc.subject.meshTrachea - Drug Effects - Enzymologyen_US
dc.titleInhibition of airway smooth muscle tone by a phorbol ester in the guinea pig trachea: Role of epithelium and receptor reserve of the contractile agenten_US
dc.typeArticleen_US
dc.identifier.emailVanhoutte, PM:vanhoutt@hku.hken_US
dc.identifier.authorityVanhoutte, PM=rp00238en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid1920116-
dc.identifier.scopuseid_2-s2.0-0025836588en_US
dc.identifier.volume259en_US
dc.identifier.issue1en_US
dc.identifier.spage198en_US
dc.identifier.epage204en_US
dc.identifier.isiWOS:A1991GK92400028-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridMorrison, KJ=7102484828en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

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