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Article: Effects of S9977 on adrenergic neurotransmission

TitleEffects of S9977 on adrenergic neurotransmission
Authors
Issue Date1993
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/vph
Citation
General Pharmacology, 1993, v. 24 n. 2, p. 429-434 How to Cite?
AbstractExperiments were designed to determine whether or not the putative promnesic drug S9977 (1,3,7-trimethyl 8-[3-(4-diethylaminocarbonyl-1-piperazinyl) 1-propyl]-3,7-dihydro (1H)2,6-purinedione hydrochloride) affects peripheral adrenergic neurotransmission. Rings of canine saphenous veins (without endothelium) were suspended for isometric tension recording in conventional organ chambers filled with modified Krebs-Ringer bicarbonate solution. The adrenergic nerve endings were activated with electrical impulses (9 V, 2 msec, 0.25-8 Hz). At 10-5 M, S9977 significantly reduced the contraction to 0.25, 0.5 and 1 Hz. The compound did not affect the response to higher stimulation frequencies or to exogenous noradrenaline. The inhibitory effect of S9977 was prevented by methiothepin, and not affected by atropine or 8-phenyltheophylline. Helical strips of canine saphenous veins were incubated with [3H]noradrenaline and suspended for superfusion and isometric tension recording. Under basal conditions, S9977 (10-4 M) augmented, the total 3H-overflow which was due mainly to an augmented overflow of [3H]deoxyphenylglycol (DOPEG); the extraneuronal metabolites 3,4-dihydromandelic acid (DOMA) and 3-methoxy-4-hydroxymandelic acid (VMA) were reduced. During electrical stimulation of the adrenergic nerves, S9977 (10-4 M) augmented the total 3H-overflow but reduced the contractile response; the evoked overflow of [3H]noradrenaline was not significantly affected. These experiments suggest that S9977 causes the displacement of noradrenaline from the adrenergic varicosities; most of the displaced transmitter is metabolized by intraneuronal monoamine oxidase before reaching the junctional cleft. In addition, S9977 exerts an inhibitory effect on the extraneuronal metabolism of catecholamines. S9977 does not inhibit the exocytotic release of the adrenergic neurotransmitter.
Persistent Identifierhttp://hdl.handle.net/10722/171103
ISSN
2002 Impact Factor: 0.591
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBoulanger, CMen_US
dc.contributor.authorHughes, Hen_US
dc.contributor.authorBond, RAen_US
dc.contributor.authorRafla, Een_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:12:12Z-
dc.date.available2012-10-30T06:12:12Z-
dc.date.issued1993en_US
dc.identifier.citationGeneral Pharmacology, 1993, v. 24 n. 2, p. 429-434en_US
dc.identifier.issn0306-3623en_US
dc.identifier.urihttp://hdl.handle.net/10722/171103-
dc.description.abstractExperiments were designed to determine whether or not the putative promnesic drug S9977 (1,3,7-trimethyl 8-[3-(4-diethylaminocarbonyl-1-piperazinyl) 1-propyl]-3,7-dihydro (1H)2,6-purinedione hydrochloride) affects peripheral adrenergic neurotransmission. Rings of canine saphenous veins (without endothelium) were suspended for isometric tension recording in conventional organ chambers filled with modified Krebs-Ringer bicarbonate solution. The adrenergic nerve endings were activated with electrical impulses (9 V, 2 msec, 0.25-8 Hz). At 10-5 M, S9977 significantly reduced the contraction to 0.25, 0.5 and 1 Hz. The compound did not affect the response to higher stimulation frequencies or to exogenous noradrenaline. The inhibitory effect of S9977 was prevented by methiothepin, and not affected by atropine or 8-phenyltheophylline. Helical strips of canine saphenous veins were incubated with [3H]noradrenaline and suspended for superfusion and isometric tension recording. Under basal conditions, S9977 (10-4 M) augmented, the total 3H-overflow which was due mainly to an augmented overflow of [3H]deoxyphenylglycol (DOPEG); the extraneuronal metabolites 3,4-dihydromandelic acid (DOMA) and 3-methoxy-4-hydroxymandelic acid (VMA) were reduced. During electrical stimulation of the adrenergic nerves, S9977 (10-4 M) augmented the total 3H-overflow but reduced the contractile response; the evoked overflow of [3H]noradrenaline was not significantly affected. These experiments suggest that S9977 causes the displacement of noradrenaline from the adrenergic varicosities; most of the displaced transmitter is metabolized by intraneuronal monoamine oxidase before reaching the junctional cleft. In addition, S9977 exerts an inhibitory effect on the extraneuronal metabolism of catecholamines. S9977 does not inhibit the exocytotic release of the adrenergic neurotransmitter.en_US
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/vphen_US
dc.relation.ispartofGeneral Pharmacologyen_US
dc.subject.meshAnalgesics - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshDogsen_US
dc.subject.meshElectric Stimulationen_US
dc.subject.meshMethoxyhydroxyphenylglycol - Analogs & Derivatives - Metabolismen_US
dc.subject.meshNorepinephrine - Secretionen_US
dc.subject.meshPiperazines - Pharmacologyen_US
dc.subject.meshSaphenous Vein - Drug Effects - Physiologyen_US
dc.subject.meshSynaptic Transmission - Drug Effectsen_US
dc.subject.meshVasoconstriction - Drug Effectsen_US
dc.subject.meshXanthines - Pharmacologyen_US
dc.titleEffects of S9977 on adrenergic neurotransmissionen_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.doi10.1016/0306-3623(93)90328-Uen_US
dc.identifier.pmid8387054-
dc.identifier.scopuseid_2-s2.0-0027409013en_US
dc.identifier.volume24en_US
dc.identifier.issue2en_US
dc.identifier.spage429en_US
dc.identifier.epage434en_US
dc.identifier.isiWOS:A1993KW62200028-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridBoulanger, CM=7006599024en_US
dc.identifier.scopusauthoridHughes, H=7202659303en_US
dc.identifier.scopusauthoridBond, RA=7102696356en_US
dc.identifier.scopusauthoridRafla, E=6505905564en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

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