title: Dual effects of a 2-benzylquinuclidinium derivative on α7-containing nicotinic acetylcholine receptors in rat hippocampal interneurons.
abstract: Nicotinic acetylcholine receptors (nAChRs) are widely distributed in the brain. Particularly α7-containing nAChRs, associated with several physiological roles and pathologies, are one of the most abundant. Here, we studied 2-(4-hexyloxybenzyl)-1-methylquinuclidin-1-ium iodide (designated as 8d), on ion currents elicited by choline, ICh, (Ch, a selective agonist for α7-containing nAChRs), recorded in interneurons from the stratum radiatum of the rat hippocampal CA1 region by using the whole-cell voltage-clamp technique. The 8d-concentration/Ch-response relationship exhibited high and low inhibitory affinities for α7-containing nAChRs, with IC50 values of 0.59 and 6.80 μM, respectively. Interestingly, 8d in a range of 3-10 μM exerted opposite effects: a short early potentiation and a long late inhibition of the ICh; and 8d alone elicited a non-decaying inward current. Furthermore, potentiation and inhibition of the ICh by 8d depended on the membrane potential, both being stronger at -20 than at -70 mV; indicating that 8d interacts with at least two sites into the ion channel/receptor complex: one for potentiating and another for inhibiting the α7-containing nAChRs. These results suggest that 8d may act as agonist, antagonist and positive modulator of α7-containing nAChRs in hippocampal interneurons.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Casilla 306, Correo 22, Santiago, Chile.
authors.forename: Jhon J
authors.initials: JJ
authors.lastname: López
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Casilla 306, Correo 22, Santiago, Chile. Electronic address: eperezh@uc.cl.
authors.forename: Edwin G
authors.initials: EG
authors.lastname: Pérez
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Boulevard Juriquilla 3001, Querétaro 76230, Mexico. Electronic address: garciacolunga@unam.mx.
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Colunga
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism*; D002794:Choline / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism*; D011812:Quinuclidines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C000605930:2-(4-(hexyloxy)benzyl)-1-methylquinuclidin-1-ium; D011812:Quinuclidines; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002794:Choline
keywords: 2-Benzylquinuclidine derivatives; Dual modulation; Hippocampus; Nicotinic acetylcholine receptor; α7 Alpha