Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors
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 c...
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2003
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0026895X_v63_n5_p1067_Rothlin http://hdl.handle.net/20.500.12110/paper_0026895X_v63_n5_p1067_Rothlin |
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paper:paper_0026895X_v63_n5_p1067_Rothlin2023-06-08T14:53:57Z Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors biogenic amine ion channel nicotinic receptor ondansetron recombinant receptor serotonin serotonin 3 antagonist tropisetron animal cell article cholinergic transmission controlled study Corti organ drug potency drug receptor binding neuromodulation nonhuman priority journal vestibular system Xenopus laevis Animals Electrophysiology Hair Cells Indoles Oocytes Receptors, Nicotinic Receptors, Serotonin Receptors, Serotonin, 5-HT3 Recombinant Proteins Serotonin Xenopus laevis 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. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0026895X_v63_n5_p1067_Rothlin http://hdl.handle.net/20.500.12110/paper_0026895X_v63_n5_p1067_Rothlin |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
biogenic amine ion channel nicotinic receptor ondansetron recombinant receptor serotonin serotonin 3 antagonist tropisetron animal cell article cholinergic transmission controlled study Corti organ drug potency drug receptor binding neuromodulation nonhuman priority journal vestibular system Xenopus laevis Animals Electrophysiology Hair Cells Indoles Oocytes Receptors, Nicotinic Receptors, Serotonin Receptors, Serotonin, 5-HT3 Recombinant Proteins Serotonin Xenopus laevis |
| spellingShingle |
biogenic amine ion channel nicotinic receptor ondansetron recombinant receptor serotonin serotonin 3 antagonist tropisetron animal cell article cholinergic transmission controlled study Corti organ drug potency drug receptor binding neuromodulation nonhuman priority journal vestibular system Xenopus laevis Animals Electrophysiology Hair Cells Indoles Oocytes Receptors, Nicotinic Receptors, Serotonin Receptors, Serotonin, 5-HT3 Recombinant Proteins Serotonin Xenopus laevis Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors |
| topic_facet |
biogenic amine ion channel nicotinic receptor ondansetron recombinant receptor serotonin serotonin 3 antagonist tropisetron animal cell article cholinergic transmission controlled study Corti organ drug potency drug receptor binding neuromodulation nonhuman priority journal vestibular system Xenopus laevis Animals Electrophysiology Hair Cells Indoles Oocytes Receptors, Nicotinic Receptors, Serotonin Receptors, Serotonin, 5-HT3 Recombinant Proteins Serotonin Xenopus laevis |
| description |
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. |
| title |
Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors |
| title_short |
Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors |
| title_full |
Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors |
| title_fullStr |
Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors |
| title_full_unstemmed |
Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors |
| title_sort |
direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors |
| publishDate |
2003 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0026895X_v63_n5_p1067_Rothlin http://hdl.handle.net/20.500.12110/paper_0026895X_v63_n5_p1067_Rothlin |
| _version_ |
1768544767199674368 |