title: Oseltamivir blocks human neuronal nicotinic acetylcholine receptor-mediated currents.
abstract: The effects of oseltamivir, a neuraminidase inhibitor, were tested on the function of neuronal nicotinic acetylcholine receptors (nAChRs) in a neuroblastoma cell line IMR32 derived from human peripheral neurons and on recombinant human α3β4 nAChRs expressed in HEK cells. IMR32 cells predominately express α3β4 nAChRs. Nicotine (nic, 30 μm)-evoked currents recorded at -90 mV in IMR32 cells using the whole-cell patch clamp technique were reversibly blocked by oseltamivir in a concentration-dependent manner. In contrast, an active metabolite of oseltamivir, oseltamivir carboxylate (OC) at 30 μm had little effect on the nic-evoked currents. Oseltamivir also blocked nic-evoked currents derived from HEK cells with recombinant α3β4 nAChRs. This blockade was voltage-dependent with 10, 30 and 100 μm oseltamivir inhibiting ~50% at -100, -60 and -40 mV, respectively. Non-inactivating currents in IMR32 cells and in HEK cells with α3β4 nAChRs, which were evoked by an endogenous nicotinic agonist, ACh (5 μm), were reversibly blocked by oseltamivir. These data demonstrate that oseltamivir blocks nAChRs, presumably via binding to a site in the channel pore.
authors: Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, Chikusa, Japan.
authors: Katsuhiko
authors: K
authors: Muraki
authors: Noriyuki
authors: N
authors: Hatano
authors: Hiroka
authors: H
authors: Suzuki
authors: Yukiko
authors: Y
authors: Muraki
authors: Yui
authors: Y
authors: Iwajima
authors: Yasuhiro
authors: Y
authors: Maeda
authors: Hideki
authors: H
authors: Ono
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D053139:Oseltamivir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; C403530:nicotinic receptor alpha3beta4; D053139:Oseltamivir; D009538:Nicotine; C535162:oseltamivir carboxylate; D000109:Acetylcholine