Enhancement of purinergic neurotransmission by galantamine and other acetylcholinesterase inhibitors in the rat vas deferens

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dc.contributor.authorCaricati-Neto, A.
dc.contributor.authorD'angelo, LCA
dc.contributor.authorReuter, H.
dc.contributor.authorJurkiewicz, N. H.
dc.contributor.authorGarcia, A. G.
dc.contributor.authorJurkiewicz, A.
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Autonoma Madrid
dc.contributor.institutionHosp Princesa
dc.date.accessioned2016-01-24T12:37:26Z
dc.date.available2016-01-24T12:37:26Z
dc.date.issued2004-10-25
dc.description.abstractGalantamine, a mild acetylcholinesterase inhibitor and an allosteric ligand of nicotinic receptors, enhanced in a concentration-dependent manner the amplitude of purinergic twitch contractions of the electrically stimulated rat vas deferens (0.2 Hz, 1 ms, 60 V). Other acetylcholinesterase inhibitors also increased the twitches, showing a hierarchy of potencies of galantamine>physostigmine >tacrine>rivastigmine=donepezil. the potentiations seem to be unrelated to the ability to inhibit acetylcholinesterase, since the hierarchy of potencies to block the enzyme in vas deferens was tacrine>physostigmine>rivastigmine>donepezil>galantamine. Acetylcholine also increased the twitches; such effect was produced by a low range of concentrations of acetylcholine (10(-10)-10(-7) M). This facilitatory effect of acetylcholine on twitches was significantly potentiated by galantamine (10(-7)-10(-6) M), but not by rivastigmine or donepezil. A striking enhancement of twitches was also caused by charybdotoxin, a blocker of high-conductance Ca2+-activated K+ channels, and by 4-aminopyridine, a non-specific blocker of K+ channels; in addition, apamin, a blocker of small-conductance Ca2+-activated K+ channels, induced a lower potentiation. the antagonist mecamylamine (10(-7)-10(-6) M) reduced by 80% the potentiation by galantamine, indicating the involvement of nicotinic receptors. Therefore, it is suggested that, besides an inhibition of acetylcholinesterase, some additional mechanisms, such as blockade of Ca2+-dependent K+ channels, or activation of nicotinic receptors of nerve terminals, might be involved in twitch potentiation. These results are relevant in the context of the clinical use of galantamine to improve cognition and behaviour in patients with Alzheimer's disease. (C) 2004 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Pharmacol, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Autonoma Madrid, Inst Teofilo Hernando, Dept Pharmacol, Fac Med, E-28049 Madrid, Spain
dc.description.affiliationHosp Princesa, Serv Farmacol Clin, Madrid 28006, Spain
dc.description.affiliationHosp Princesa, Inst Gerontol, Madrid 28006, Spain
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Pharmacol, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent191-201
dc.identifierhttp://dx.doi.org/10.1016/j.ejphar.2004.09.034
dc.identifier.citationEuropean Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 503, n. 1-3, p. 191-201, 2004.
dc.identifier.doi10.1016/j.ejphar.2004.09.034
dc.identifier.issn0014-2999
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/27983
dc.identifier.wosWOS:000225058600027
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofEuropean Journal of Pharmacology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectpurinergic neurotransmissionen
dc.subjectgalantamineen
dc.subjectvas deferensen
dc.titleEnhancement of purinergic neurotransmission by galantamine and other acetylcholinesterase inhibitors in the rat vas deferensen
dc.typeinfo:eu-repo/semantics/article
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