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- Scopus: eid_2-s2.0-0026098901
- PMID: 1899121
- WOS: WOS:A1991ET54200008
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Article: Inhibition of endothelium-dependent relaxations by phorbol myristate acetate in canine coronary arteries: Role of a pertussis toxin-sensitive G-protein
Title | Inhibition of endothelium-dependent relaxations by phorbol myristate acetate in canine coronary arteries: Role of a pertussis toxin-sensitive G-protein |
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Authors | |
Issue Date | 1991 |
Publisher | American 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? |
Abstract | Activation 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 Identifier | http://hdl.handle.net/10722/171033 |
ISSN | 2023 Impact Factor: 3.1 2023 SCImago Journal Rankings: 0.829 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Flavahan, NA | en_US |
dc.contributor.author | Shimokawa, H | en_US |
dc.contributor.author | Vanhoutte, PM | en_US |
dc.date.accessioned | 2012-10-30T06:11:54Z | - |
dc.date.available | 2012-10-30T06:11:54Z | - |
dc.date.issued | 1991 | en_US |
dc.identifier.citation | Journal Of Pharmacology And Experimental Therapeutics, 1991, v. 256 n. 1, p. 50-55 | en_US |
dc.identifier.issn | 0022-3565 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/171033 | - |
dc.description.abstract | Activation 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.language | eng | en_US |
dc.publisher | American Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.org | en_US |
dc.relation.ispartof | Journal of Pharmacology and Experimental Therapeutics | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Coronary Vessels - Drug Effects - Physiology | en_US |
dc.subject.mesh | Dogs | en_US |
dc.subject.mesh | Dose-Response Relationship, Drug | en_US |
dc.subject.mesh | Endothelium - Drug Effects - Physiology | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Gtp-Binding Proteins - Metabolism - Physiology | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Muscle Relaxation - Drug Effects | en_US |
dc.subject.mesh | Muscle, Smooth, Vascular - Drug Effects - Physiology | en_US |
dc.subject.mesh | Nitric Oxide - Physiology | en_US |
dc.subject.mesh | Pertussis Toxin | en_US |
dc.subject.mesh | Phorbol Esters - Pharmacology | en_US |
dc.subject.mesh | Tetradecanoylphorbol Acetate - Pharmacology | en_US |
dc.subject.mesh | Virulence Factors, Bordetella - Antagonists & Inhibitors - Pharmacology | en_US |
dc.title | Inhibition of endothelium-dependent relaxations by phorbol myristate acetate in canine coronary arteries: Role of a pertussis toxin-sensitive G-protein | en_US |
dc.type | Article | en_US |
dc.identifier.email | Vanhoutte, PM:vanhoutt@hku.hk | en_US |
dc.identifier.authority | Vanhoutte, PM=rp00238 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.pmid | 1899121 | - |
dc.identifier.scopus | eid_2-s2.0-0026098901 | en_US |
dc.identifier.volume | 256 | en_US |
dc.identifier.issue | 1 | en_US |
dc.identifier.spage | 50 | en_US |
dc.identifier.epage | 55 | en_US |
dc.identifier.isi | WOS:A1991ET54200008 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Flavahan, NA=7006398882 | en_US |
dc.identifier.scopusauthorid | Shimokawa, H=16684837100 | en_US |
dc.identifier.scopusauthorid | Vanhoutte, PM=7202304247 | en_US |
dc.identifier.issnl | 0022-3565 | - |