Vázquez-Gómeza, E, Arias, HR, Miranda-Morales, M, Mihailescu, S, Feuerbach, Dominik and García-Colunga, J (2014) Bupropion-induced inhibition of α7 nicotinic acetylcholine receptors expressed in heterologous cells, neurons from dorsal raphe nucleus and hippocampus. EuropeanJournalofPharmacology.

Abstract

The pharmacological activity of the antidepressant and smoking-cessation compound bupropion (BP) was determined in nicotinic acetylcholine receptors (nAChRs) expressed in heterologous cells and then compared to that in neurons. The inhibitory potency of BP was determined on GH3-α7 cells by Ca2+ influx assays, whereas its binding affinity was determined by [3H]imipramine competition binding using SHSY5Y-α7 cell membranes. Additionally, the effects of BP on ion currents elicited by acetylcholine (ACh) and choline (Ch) on neurons from the dorsal raphe nucleus and interneurons from the stratus radiatum of the hippocampal CA1 region were examined by using the whole-cell voltage-clamp technique. The fast component of ACh- and Ch-induced currents from both brain regions were inhibited by methyllycaconitine, indicating the participation of 7-containing nAChRs. Additionally, both agonist-induced currents, in each brain region, were reversibly inhibited by BP at coincident concentrations with its inhibitory potency (IC50 = 54 µM) and binding affinity (Ki = 63 µM) for the α7 nAChRs in heterologous cells. Moreover, Ch-induced currents in hippocampal interneurons were partially inhibited by 10 µM BP, a concentration that could be reached in the brain during clinical administration. This work may help to understand the mechanisms of actions of BP at the neuronal and molecular levels related with its therapeutic actions on depression and for smoking cessation.

Item Type:	Article
Date Deposited:	26 Apr 2016 23:46
Last Modified:	26 Apr 2016 23:46
URI:	https://oak.novartis.com/id/eprint/10899