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Titolo:
Antagonism of nicotinic acetylcholine receptors by inhibitors of monoamineuptake
Autore:
Lopez-Valdes, HE; Garcia-Colunga, J;
Indirizzi:
Univ Nacl Autonoma Mexico, Ctr Neurobiol, Juriquilla 76001, Queretaro, Mexico Univ Nacl Autonoma Mexico Juriquilla Queretaro Mexico 76001 etaro, Mexico
Titolo Testata:
MOLECULAR PSYCHIATRY
fascicolo: 5, volume: 6, anno: 2001,
pagine: 511 - 519
SICI:
1359-4184(200109)6:5<511:AONARB>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRICYCLIC ANTI-DEPRESSANTS; NONCOMPETITIVE INHIBITORS; FLUOXETINE PROZAC; ION-CHANNEL; HUMAN BRAIN; BLOCKAGE; MUSCLE; 5-HYDROXYTRYPTAMINE; ANTIDEPRESSANTS; CELLS;
Keywords:
serotonin transporters; antidepressants; cholinergic-serotonergic interaction; nicotinic receptor modulation; Xenopus oocytes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Garcia-Colunga, J Univ Nacl Autonoma Mexico, Ctr Neurobiol, Campus Juriquilla,Apartado Postal 1-1141, Juriquilla 76001, Queretaro, Mexico Univ Nacl Autonoma Mexico Campus Juriquilla,Apartado Postal 1-1141 Juriquilla Queretaro Mexico 76001
Citazione:
H.E. Lopez-Valdes e J. Garcia-Colunga, "Antagonism of nicotinic acetylcholine receptors by inhibitors of monoamineuptake", MOL PSYCHI, 6(5), 2001, pp. 511-519

Abstract

A study was made of the effects of several monoamine-uptake inhibitors on membrane currents elicited by acetylcholine (ACh-currents) generated by ratneuronal alpha2 beta4 and mouse muscle nicotinic acetylcholine receptors (AChRs) expressed in Xenopus laevis oocytes. For the two types of receptors the monoamine-uptake inhibitors reduced the ACh-currents albeit to different degrees. The order of inhibitory potency was norfluoxetine > clomipramine> indatraline > fluoxetine > imipramine > zimelidine > 6-nitro-quipazine >trazodone for neuronal alpha2 beta4 AChRs, and norfluoxetine > fluoxetine > imipramine > clomipramine > indatraline > zimelidine > trazodone > 6-nitro-quipazine for muscle AChRs. Thus, the most potent inhibitor was norfluoxetine, whilst the weakest ones were trazodone, 6-nitro-quipazine and zimelidine. Effects of the tricyclic antidepressant imipramine were studied in more detail. Imipramine inhibited reversibly and non-competitively the ACh-current with a similar inhibiting potency for both neuronal alpha2 beta4 and muscle AChRs. The half-inhibitory concentrations of imipramine were 3.65 +/-0.30 muM for neuronal alpha2 beta4 and 5.57 +/- 0.19 muM for muscle receptors. The corresponding Hill coefficients were 0.73 and 1.2 respectively. The inhibition of imipramine was slightly voltage-dependent, with electric distances of similar to0.10 and similar to0.12 for neuronal alpha2 beta4 and muscle AChRs respectively. Moreover, imipramine accelerated the rate of decay of ACh-currents of both muscle and neuronal AChRs. The ACh-current inhibition was stronger when oocytes, expressing neuronal alpha2 beta4 or musclereceptors, were preincubated with imipramine alone than when it was applied after the ACh-current had been generated, suggesting that imipramine actsalso on non-activated or closed AChRs. We conclude that monoamine-uptake inhibitors reduce ACh-currents and that imipramine regulates reversibly and noncompetitively neuronal alpha2 beta4 and muscle AChRs through similar mechanisms, perhaps by interacting externally on a non-conducting state of theAChR and by blocking the open receptor-channel complex close to the vestibule of the channel. These studies may be important for understanding the regulation of AChRs as well as for understanding antidepressant- and side-effects of monoamine-uptake inhibitors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/02/20 alle ore 03:01:58