Fluoxetine is used in the treatment of a variety of clinical disorders including depression and obesity, and of cocaine detoxification or alcoholism. It is generally believed that fluoxetine exerts its clinical effects because it selectively blocks 5-hydroxytryptamine (5HT) reuptake into nerve terminals. In here we describe that fluoxetine antagonized the neuronal homomeric alpha(7) nicotinic acetylcholine receptors (nAChR) expressed in Xenopus oocytes, with an IC50 of 43 mu M, when fluoxetine was coapplied with ACh, and of 1.6 mu M when the oocytes were pretreated briefly with fluoxetine. A similar block occurred in oocytes expressing L247T alpha(7) mutant nAChR. Furthermore, blockage of mutant alpha(7) receptors appeared non-competitive and was stronger with cell membrane hyperpolarization. Cell-attached single channel recordings in oocytes expressing L247T alpha(7) mutant nAChR showed that the voltage-dependence of the blockage by fluoxetine could be due to a drastic decrease in channel opening frequency accompanied by marked channel flickering and reduced channel conductance. We conclude that fluoxetine behaves as a reversible blocker of both wild and mutant alpha(7) receptors; and that the Leu-247T mutation in the channel domain renders the blockage of alpha(7) nAChR by fluoxetine voltage-dependent. These effects of fluoxetine on alpha(7) receptors may be clinically important

Effects of fluoxetine (Prozac) on wild and mutant neuronal alpha7 nicotinic receptors / Maggi, Laura; Palma, Eleonora; Eusebi, Fabrizio; R., Miledi. - In: MOLECULAR PSYCHIATRY. - ISSN 1359-4184. - STAMPA. - 3:(1998), pp. 350-355. [10.1038/sj.mp.4000392]

Effects of fluoxetine (Prozac) on wild and mutant neuronal alpha7 nicotinic receptors

MAGGI, Laura;PALMA, Eleonora;EUSEBI, Fabrizio;
1998

Abstract

Fluoxetine is used in the treatment of a variety of clinical disorders including depression and obesity, and of cocaine detoxification or alcoholism. It is generally believed that fluoxetine exerts its clinical effects because it selectively blocks 5-hydroxytryptamine (5HT) reuptake into nerve terminals. In here we describe that fluoxetine antagonized the neuronal homomeric alpha(7) nicotinic acetylcholine receptors (nAChR) expressed in Xenopus oocytes, with an IC50 of 43 mu M, when fluoxetine was coapplied with ACh, and of 1.6 mu M when the oocytes were pretreated briefly with fluoxetine. A similar block occurred in oocytes expressing L247T alpha(7) mutant nAChR. Furthermore, blockage of mutant alpha(7) receptors appeared non-competitive and was stronger with cell membrane hyperpolarization. Cell-attached single channel recordings in oocytes expressing L247T alpha(7) mutant nAChR showed that the voltage-dependence of the blockage by fluoxetine could be due to a drastic decrease in channel opening frequency accompanied by marked channel flickering and reduced channel conductance. We conclude that fluoxetine behaves as a reversible blocker of both wild and mutant alpha(7) receptors; and that the Leu-247T mutation in the channel domain renders the blockage of alpha(7) nAChR by fluoxetine voltage-dependent. These effects of fluoxetine on alpha(7) receptors may be clinically important
1998
alpha(7) mutant receptor, Xenopus oocytes, fluoxetine, neuronal nicotinic receptors
01 Pubblicazione su rivista::01a Articolo in rivista
Effects of fluoxetine (Prozac) on wild and mutant neuronal alpha7 nicotinic receptors / Maggi, Laura; Palma, Eleonora; Eusebi, Fabrizio; R., Miledi. - In: MOLECULAR PSYCHIATRY. - ISSN 1359-4184. - STAMPA. - 3:(1998), pp. 350-355. [10.1038/sj.mp.4000392]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/247660
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 48
  • ???jsp.display-item.citation.isi??? 45
social impact