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Article: Biphasic release of endothelium-derived relaxing factor(s) by acetylcholine from perfused canine femoral arteries. Characterization of muscarinic receptors

TitleBiphasic release of endothelium-derived relaxing factor(s) by acetylcholine from perfused canine femoral arteries. Characterization of muscarinic receptors
Authors
Issue Date1987
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, 1987, v. 240 n. 3, p. 802-808 How to Cite?
AbstractExperiments were designed to compare the release of endothelium-derived relaxing factor(s) in response to various muscarinic receptor agonists from canine femoral arteries mounted in organ chambers or perfused in a bioassay system. In rings of femoral arteries, suspended for isometric tension recording in organ chambers, acetylcholine induced endothelium-dependent relaxations during contractions evoked by prostaglandin F(2a). Atropine and pirenzepine antagonized these relaxations in a competitive manner, atropine with a higher affinity (K(B) = 1.9 x 10-9 M) than pirenzepine (K(B) = 5.4 x 10-7 M). Carbachol and McN-A-323 also evoked endothelium-dependent relaxations, and pirenzepine inhibited these responses with a similar low potency. The order of relative potency of the agonists in organ chamber studies was acetylcholine = carbachol >> McN-A-343. Isolated segments of femoral arteries with endothelium were perfused (2 ml/min) with modified Krebs-Ringer-bicarbonate solution containing indomethacin; the perfusate was bioassayed for endothelium-derived relaxing factor(s) by means of a ring of coronary artery without endothelium. When infused above but not below the femoral artery, low concentrations (10-8-10-7 M) of acetylcholine caused transient relaxations of the bioassay ring contracted with prostaglandin F(2a); higher concentrations of acetylcholine caused sustained decreases in tension. Atropine inhibited the two phases of the concentration-relaxation curve with similar potencies. Pirenzepine inhibited both phases in a competitive manner but exhibited significantly higher potency against the first- (ED50, 1.9 x 10-9 M) than against the second-phase responses (ED50, 2.1 x 10-7 M). Compound McN-A-343 induced only transient decreases in tension, whereas carbachol caused sustained relaxations. The order of relative potency of the agonists in bioassay studies was McN-A-343 = acetylcholine >> carbachol (for transient responses) and acetylcholine = carbachol >> McN-A-343 (for sustained responses). These experiments indicate that, in isolated femoral arterial rings studied in the organ chamber, muscarinic receptors with low affinity for pirenzepine appear to be involved in the endothelium-dependent relaxations evoked by various muscarinic receptor agonists. In perfused segments of the same artery, acetylcholine stimulates the intraluminal release of endothelium-derived relaxing factor(s) in a manner that produces a biphasic concentration-relaxation curve in a superfused bioassay preparation. Although this system does not allow rigorous receptor analysis, it is tentatively postulated that muscarinic receptors with different properties mediate the two phases of the response.
Persistent Identifierhttp://hdl.handle.net/10722/170839
ISSN
2015 Impact Factor: 3.76
2015 SCImago Journal Rankings: 1.847
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorRubanyi, GMen_US
dc.contributor.authorMckinney, Men_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:11:04Z-
dc.date.available2012-10-30T06:11:04Z-
dc.date.issued1987en_US
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 1987, v. 240 n. 3, p. 802-808en_US
dc.identifier.issn0022-3565en_US
dc.identifier.urihttp://hdl.handle.net/10722/170839-
dc.description.abstractExperiments were designed to compare the release of endothelium-derived relaxing factor(s) in response to various muscarinic receptor agonists from canine femoral arteries mounted in organ chambers or perfused in a bioassay system. In rings of femoral arteries, suspended for isometric tension recording in organ chambers, acetylcholine induced endothelium-dependent relaxations during contractions evoked by prostaglandin F(2a). Atropine and pirenzepine antagonized these relaxations in a competitive manner, atropine with a higher affinity (K(B) = 1.9 x 10-9 M) than pirenzepine (K(B) = 5.4 x 10-7 M). Carbachol and McN-A-323 also evoked endothelium-dependent relaxations, and pirenzepine inhibited these responses with a similar low potency. The order of relative potency of the agonists in organ chamber studies was acetylcholine = carbachol >> McN-A-343. Isolated segments of femoral arteries with endothelium were perfused (2 ml/min) with modified Krebs-Ringer-bicarbonate solution containing indomethacin; the perfusate was bioassayed for endothelium-derived relaxing factor(s) by means of a ring of coronary artery without endothelium. When infused above but not below the femoral artery, low concentrations (10-8-10-7 M) of acetylcholine caused transient relaxations of the bioassay ring contracted with prostaglandin F(2a); higher concentrations of acetylcholine caused sustained decreases in tension. Atropine inhibited the two phases of the concentration-relaxation curve with similar potencies. Pirenzepine inhibited both phases in a competitive manner but exhibited significantly higher potency against the first- (ED50, 1.9 x 10-9 M) than against the second-phase responses (ED50, 2.1 x 10-7 M). Compound McN-A-343 induced only transient decreases in tension, whereas carbachol caused sustained relaxations. The order of relative potency of the agonists in bioassay studies was McN-A-343 = acetylcholine >> carbachol (for transient responses) and acetylcholine = carbachol >> McN-A-343 (for sustained responses). These experiments indicate that, in isolated femoral arterial rings studied in the organ chamber, muscarinic receptors with low affinity for pirenzepine appear to be involved in the endothelium-dependent relaxations evoked by various muscarinic receptor agonists. In perfused segments of the same artery, acetylcholine stimulates the intraluminal release of endothelium-derived relaxing factor(s) in a manner that produces a biphasic concentration-relaxation curve in a superfused bioassay preparation. Although this system does not allow rigorous receptor analysis, it is tentatively postulated that muscarinic receptors with different properties mediate the two phases of the response.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.mesh(4-(M-Chlorophenylcarbamoyloxy)-2-Butynyl)Trimethylammonium Chloride - Pharmacologyen_US
dc.subject.meshAcetylcholine - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAtropine - Pharmacologyen_US
dc.subject.meshCarbachol - Pharmacologyen_US
dc.subject.meshDogsen_US
dc.subject.meshEndothelium - Drug Effects - Secretionen_US
dc.subject.meshFemaleen_US
dc.subject.meshFemoral Artery - Drug Effects - Secretionen_US
dc.subject.meshMaleen_US
dc.subject.meshNitric Oxideen_US
dc.subject.meshPirenzepine - Pharmacologyen_US
dc.subject.meshReceptors, Muscarinic - Drug Effects - Physiologyen_US
dc.subject.meshVasodilator Agents - Secretionen_US
dc.titleBiphasic release of endothelium-derived relaxing factor(s) by acetylcholine from perfused canine femoral arteries. Characterization of muscarinic receptorsen_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.pmid2435886-
dc.identifier.scopuseid_2-s2.0-0023122644en_US
dc.identifier.volume240en_US
dc.identifier.issue3en_US
dc.identifier.spage802en_US
dc.identifier.epage808en_US
dc.identifier.isiWOS:A1987G571800016-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridRubanyi, GM=7005517991en_US
dc.identifier.scopusauthoridMckinney, M=35447338700en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

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