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

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

Autor Caricati-Neto, A. Google Scholar
D'angelo, LCA Google Scholar
Reuter, H. Google Scholar
Jurkiewicz, N. H. Google Scholar
Garcia, A. G. Google Scholar
Jurkiewicz, A. Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Univ Autonoma Madrid
Hosp Princesa
Resumo Galantamine, 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.
Assunto purinergic neurotransmission
vas deferens
Idioma Inglês
Data 2004-10-25
Publicado em European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 503, n. 1-3, p. 191-201, 2004.
ISSN 0014-2999 (Sherpa/Romeo, fator de impacto)
Editor Elsevier B.V.
Extensão 191-201
Fonte http://dx.doi.org/10.1016/j.ejphar.2004.09.034
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000225058600027
URI http://repositorio.unifesp.br/handle/11600/27983

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