Direct interaction of serotonin type 3 receptor ligands with recombinant and native alpha 9 alpha 10-containing nicotinic cholinergic receptors.
Direct interaction of serotonin type 3 receptor ligands with recombinant and native alpha 9 alpha 10-containing nicotinic cholinergic receptors.
复制标题
3 型血清素受体配体与重组和天然含 α 9 α 10 烟碱胆碱能受体的直接相互作用。
作者：
C. Rothlin;M. Lioudyno;Ana F. Silbering;P. Plazas;M. Casati;E. Katz;P. Guth;A. Elgoyhen
在目前的工作中，我们表征了5-羟色胺3型受体配体对重组和天然的含有α9α10的烟碱型乙酰胆碱受体(NAChRs)的影响。我们的结果表明，重组α9α10 nAChR与5-羟色胺(3)配体门控离子通道具有显著的药理作用。因此，5-羟色胺(3)受体拮抗剂以托烷司琼(IC(50)，70.1+/-0.9 nM)和恩丹西酮(IC(50)，0.6+/-0.1微米)=MDL 72222(IC(50)，0.7+/-0.1微米)的效力顺序阻断非洲爪哇卵母细胞ACh诱发电流。尽管5-羟色胺不能引起注射α9α10的卵母细胞的反应，但它以非竞争性和电压依赖的方式阻断重组的α9α10受体(IC(50)，5.4+/-0.6微米)。另一方面，我们证明了重组受体的这些特性与青蛙球囊毛细胞中含有α9α10的nAChR的特性在体内相关。讨论了生物胺5-羟色胺可能作为前庭器官和Corti器官胆碱能传出传递的神经调节剂的可能性。
In the present work, we characterized the effects of serotonin type 3 receptor ligands on recombinant and native alpha 9 alpha 10-containing nicotinic acetylcholine receptors (nAChRs). Our results indicate that the recombinant alpha 9 alpha 10 nAChR shares striking pharmacological properties with 5-HT(3) ligand-gated ion channels. Thus, 5-HT(3) receptor antagonists block ACh-evoked currents in alpha 9 alpha 10-injected Xenopus laevis oocytes with a rank order of potency of tropisetron (IC(50), 70.1 +/- 0.9 nM) > ondansetron (IC(50), 0.6 +/- 0.1 microM) = MDL 72222 (IC(50), 0.7 +/- 0.1 microM). Although serotonin does not elicit responses in alpha 9 alpha 10-injected oocytes, it blocks recombinant alpha 9 alpha 10 receptors in a noncompetitive and voltage-dependent manner (IC(50), 5.4 +/- 0.6 microM). On the other hand, we demonstrate an in vivo correlate of these properties of the recombinant receptor, with those of the alpha 9 alpha 10-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.