RT Journal Article
SR Electronic
T1 Direct Interaction of Serotonin Type 3 Receptor Ligands with Recombinant and Native α9α10-Containing Nicotinic Cholinergic Receptors
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1067
OP 1074
DO 10.1124/mol.63.5.1067
VO 63
IS 5
A1 Carla V. Rothlin
A1 Maria I. Lioudyno
A1 Ana F. Silbering
A1 Paola V. Plazas
A1 Marı́a E. Gomez Casati
A1 Eleonora Katz
A1 Paul S. Guth
A1 A. Belén Elgoyhen
YR 2003
UL http://molpharm.aspetjournals.org/content/63/5/1067.abstract
AB In the present work, we characterized the effects of serotonin type 3 receptor ligands on recombinant and native α9α10-containing nicotinic acetylcholine receptors (nAChRs). Our results indicate that the recombinant α9α10 nAChR shares striking pharmacological properties with 5-HT3 ligand-gated ion channels. Thus, 5-HT3 receptor antagonists block ACh-evoked currents in α9α10-injected Xenopus laevis oocytes with a rank order of potency of tropisetron (IC50, 70.1 ± 0.9 nM) > ondansetron (IC50, 0.6 ± 0.1 μM) = MDL 72222 (IC50, 0.7 ± 0.1 μM). Although serotonin does not elicit responses in α9α10-injected oocytes, it blocks recombinant α9α10 receptors in a noncompetitive and voltage-dependent manner (IC50, 5.4 ± 0.6 μM). On the other hand, we demonstrate an in vivo correlate of these properties of the recombinant receptor, with those of the α9α10-containing nAChR of frog saccular hair cells. The possibility that the biogenic amine serotonin might act as a neuromodulator of the cholinergic efferent transmission in the vestibular apparatus and in the organ of Corti is discussed. The American Society for Pharmacology and Experimental Therapeutics