File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Inhibition of endothelium-dependent relaxations by phorbol myristate acetate in canine coronary arteries: Role of a pertussis toxin-sensitive G-protein

TitleInhibition of endothelium-dependent relaxations by phorbol myristate acetate in canine coronary arteries: Role of a pertussis toxin-sensitive G-protein
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. 256 n. 1, p. 50-55 How to Cite?
AbstractActivation of protein kinase C by phorbol esters inhibits the endothelium-dependent relaxations evoked by certain stimuli. The release of endothelium-derived relaxing factor can be evoked by a number of distinct subcellular processes, including activation of a pertussis toxin-sensitive G-protein. The aim of the present study was to determine whether or not the inhibitory effect of phorbol esters on endothelial function was associated with inhibition of the pertussis toxin-sensitive pathway. Rings of canine coronary artery were suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution, gassed with 95% O2-5% CO2 (37°C). Treatment of arterial rings with pertussis toxin (100 ng/ml) or with phorbol myristate acetate (PMA, 10-8 M) inhibited the endothelium-dependent relaxations produced by UK 14,304, an alpha-2 adrenergic agonist, leukotriene C4 or by NaF, a direct activator of G proteins, but did not affect the endothelium-dependent relaxations produced by bradykinin or by A23187. If the arterial rings were first treated with pertussis toxin, PMA (10-8 M) no longer inhibited the endothelium-dependent relaxations to NaF. Increasing the concentration of PMA (to 3 x 10-8 and 10-7 M) caused inhibition of responses to bradykinin. At higher concentrations, PMA (3 x 10-7 and 10-6) also inhibited the relaxations evoked by A23187. The endothelium-independent relaxations evoked by nitroglycerin were not affected by PMA (10-8 to 10-6) These results suggest that in canine coronary arteries, endothelial leukotriene and alpha-2 adrenergic receptors are linked to a pertussis toxin-sensitive G-protein that stimulates the release of endothelium-derived relaxing factor(s). At low concentrations, PMA inhibits selectively this pertussis toxin-sensitive pathway, possibly by inhibiting the function of the pertussis toxin-sensitive G-protein in the endothelial cells.
Persistent Identifierhttp://hdl.handle.net/10722/171033
ISSN
2015 Impact Factor: 3.76
2015 SCImago Journal Rankings: 1.847
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFlavahan, NAen_US
dc.contributor.authorShimokawa, Hen_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:11:54Z-
dc.date.available2012-10-30T06:11:54Z-
dc.date.issued1991en_US
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 1991, v. 256 n. 1, p. 50-55en_US
dc.identifier.issn0022-3565en_US
dc.identifier.urihttp://hdl.handle.net/10722/171033-
dc.description.abstractActivation of protein kinase C by phorbol esters inhibits the endothelium-dependent relaxations evoked by certain stimuli. The release of endothelium-derived relaxing factor can be evoked by a number of distinct subcellular processes, including activation of a pertussis toxin-sensitive G-protein. The aim of the present study was to determine whether or not the inhibitory effect of phorbol esters on endothelial function was associated with inhibition of the pertussis toxin-sensitive pathway. Rings of canine coronary artery were suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution, gassed with 95% O2-5% CO2 (37°C). Treatment of arterial rings with pertussis toxin (100 ng/ml) or with phorbol myristate acetate (PMA, 10-8 M) inhibited the endothelium-dependent relaxations produced by UK 14,304, an alpha-2 adrenergic agonist, leukotriene C4 or by NaF, a direct activator of G proteins, but did not affect the endothelium-dependent relaxations produced by bradykinin or by A23187. If the arterial rings were first treated with pertussis toxin, PMA (10-8 M) no longer inhibited the endothelium-dependent relaxations to NaF. Increasing the concentration of PMA (to 3 x 10-8 and 10-7 M) caused inhibition of responses to bradykinin. At higher concentrations, PMA (3 x 10-7 and 10-6) also inhibited the relaxations evoked by A23187. The endothelium-independent relaxations evoked by nitroglycerin were not affected by PMA (10-8 to 10-6) These results suggest that in canine coronary arteries, endothelial leukotriene and alpha-2 adrenergic receptors are linked to a pertussis toxin-sensitive G-protein that stimulates the release of endothelium-derived relaxing factor(s). At low concentrations, PMA inhibits selectively this pertussis toxin-sensitive pathway, possibly by inhibiting the function of the pertussis toxin-sensitive G-protein in the endothelial cells.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.meshAnimalsen_US
dc.subject.meshCoronary Vessels - Drug Effects - Physiologyen_US
dc.subject.meshDogsen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshEndothelium - Drug Effects - Physiologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshGtp-Binding Proteins - Metabolism - Physiologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMuscle Relaxation - Drug Effectsen_US
dc.subject.meshMuscle, Smooth, Vascular - Drug Effects - Physiologyen_US
dc.subject.meshNitric Oxide - Physiologyen_US
dc.subject.meshPertussis Toxinen_US
dc.subject.meshPhorbol Esters - Pharmacologyen_US
dc.subject.meshTetradecanoylphorbol Acetate - Pharmacologyen_US
dc.subject.meshVirulence Factors, Bordetella - Antagonists & Inhibitors - Pharmacologyen_US
dc.titleInhibition of endothelium-dependent relaxations by phorbol myristate acetate in canine coronary arteries: Role of a pertussis toxin-sensitive G-proteinen_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.pmid1899121-
dc.identifier.scopuseid_2-s2.0-0026098901en_US
dc.identifier.volume256en_US
dc.identifier.issue1en_US
dc.identifier.spage50en_US
dc.identifier.epage55en_US
dc.identifier.isiWOS:A1991ET54200008-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridFlavahan, NA=7006398882en_US
dc.identifier.scopusauthoridShimokawa, H=16684837100en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats