TY - JOUR T1 - Interactions between 3-(Trifluoromethyl)-3-(m-[<sup>125</sup>I]iodophenyl)diazirine and Tetracaine, Phencyclidine, or Histrionicotoxin in the<em>Torpedo</em> Species Nicotinic Acetylcholine Receptor Ion Channel JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1514 LP - 1522 DO - 10.1124/mol.59.6.1514 VL - 59 IS - 6 AU - Martin J. Gallagher AU - David C. Chiara AU - Jonathan B. Cohen Y1 - 2001/06/01 UR - http://molpharm.aspetjournals.org/content/59/6/1514.abstract N2 - 3-(Trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine ([125I]TID) and [3H]tetracaine, an aromatic amine, are noncompetitive antagonists (NCAs) of theTorpedo species nicotinic acetylcholine receptor (nAChR), which have been shown by photoaffinity labeling to bind to a common site in the ion channel in the closed state. Although tetracaine and TID bind to the same site, the amine NCAs phencyclidine (PCP) and histrionicotoxin (HTX), which are also believed to bind within the ion channel, interact competitively with tetracaine but allosterically with TID. To better characterize drug interactions within the nAChR ion channel in the closed state, we identified the amino acids photoaffinity labeled by [125I]TID in the presence of tetracaine, PCP, or HTX. In the absence of other drugs, [125I]TID reacts with αLeu-251 (αM2-9) and αVal-255 (αM2-13) and the homologous residues in each of the other subunits. None of the NCAs shifted the sites of [125I]TID labeling to other residues within the ion channel. Tetracaine inhibited [125I]TID labeling of M2-9 and M2-13 without changing the relative125I incorporation at these positions, whereas PCP and HTX each altered the pattern of [125I]TID incorporation at M2-9 and M2-13. These results indicate that tetracaine and TID bind in a mutually exclusive manner to a common site in the closed channel that is spatially separated from the binding sites for PCP and HTX. ER -