INVESTIGADORES
PLAZAS Paola Viviana
congresos y reuniones científicas
Título:
DIFFERENT SITES OF INTERACCION OF QUINOLINE DERIVATIVES WITH alpha9 alpha10 nAChRs
Autor/es:
JIMENA A. BALLESTERO; PAOLA V. PLAZAS; SEBASTIAN KRACUN; M.E. GOMEZ CASATI; JULIAN TARANDA; C.V. ROTHLIN; ELEONORA KATZ; NEIL S. MILLAR; A. BELÉN ELGOYHEN
Lugar:
Pinamar, Prov. Buenos Aires, Argentina
Reunión:
Congreso; X Congreso de la Asociación Panamericana de Bioquímica y Bilogía Molecular (PABMB), XLI Reunión Anual de la Sociedad Argentina de Bioquímica y Biología Molecular (SAIB), XX Reunión Anual de la Sociedad Argentina de Neuroquímica (SAN); 2005
Resumen:
In this study, we report the effects of the quinoline derivatives quinine (Qn), its optical isomer quinidine (Qd), and chloroquine (Cl) on á9á10 nicotinic acetylcholine receptors (nAChRs). The compounds blocked acetylcholine (ACh) evoked responses in á9á10-injected Xenopus laevis oocytes in a concentrationdependent manner, with a rank order of potency of Cl (IC50=0.39ìM) > Qn (IC50=0.97ìM) ~ Qd (IC50 =1.37ìM). Moreover, Cl blocked ACh-evoked responses on rat cochlear inner hair cells with an IC50 value of 0.13ìM. Block by Cl was purely competitive, whereas Qn inhibited ACh currents in a mixed competitive/noncompetitive manner. The competitive nature of the blockage produced by the three compounds was confirmed by equilibrium binding experiments using [H3]methyllycaconitine. Block by Qn was found to be only slightly voltage-dependent, thus precluding open-channel block as the main mechanism of interaction of quinine with á9á10 nAChRs. The present results add to the pharmacological characterization of á9á10-containing nicotinic receptors and indicate that the efferent olivocochlear system that innervates the cochlear hair cells is a target of these ototoxic antimalarial compounds.