Rothlin C V, Katz E, Verbitsky M, Elgoyhen A B
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas-Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Mol Pharmacol. 1999 Feb;55(2):248-54. doi: 10.1124/mol.55.2.248.
In the present study, we provide evidence that the alpha9 nicotinic acetylcholine receptor (nAChR) shares pharmacological properties with members of the Cys-loop family of receptors. Thus, the type A gamma-aminobutyric acid receptor antagonist bicuculline, the glycinergic antagonist strychnine, and the type 3 serotonin receptor antagonist ICS-205,930 block ACh-evoked currents in alpha9-injected Xenopus laevis oocytes with the following rank order of potency: strychnine > ICS-205,930 > bicuculline. Block by antagonists was reflected in an increase in the acetylcholine (ACh) EC50 value, with no changes in agonist maximal response or Hill coefficient, which suggests a competitive type of block. Moreover, whereas neither gamma-aminobutyric acid nor glycine modified ACh-evoked currents, serotonin blocked responses to ACh in a concentration-dependent manner. The present results suggest that the alpha9 nAChR must conserve in its primary structure some residues responsible for ligand binding common to other Cys-loop receptors. In addition, it adds further evidence that the alpha9 nAChR and the cholinergic receptor present at the base of cochlear outer hair cells have similar pharmacological properties.
在本研究中，我们提供了证据表明α9烟碱型乙酰胆碱受体（nAChR）与半胱氨酸环受体家族成员具有共同的药理学特性。因此，A型γ-氨基丁酸受体拮抗剂荷包牡丹碱、甘氨酸能拮抗剂士的宁以及3型5-羟色胺受体拮抗剂ICS-205,930能阻断注射了α9的非洲爪蟾卵母细胞中乙酰胆碱（ACh）诱发的电流，其效力顺序如下：士的宁>ICS-205,930>荷包牡丹碱。拮抗剂的阻断作用表现为乙酰胆碱（ACh）的半数有效浓度（EC50）值增加，而激动剂的最大反应或希尔系数没有变化，这表明是竞争性阻断类型。此外，虽然γ-氨基丁酸和甘氨酸都不会改变ACh诱发的电流，但5-羟色胺会以浓度依赖的方式阻断对ACh的反应。目前的结果表明，α9 nAChR在其一级结构中必须保留一些负责与其他半胱氨酸环受体共同结合配体的残基。此外，它进一步证明了α9 nAChR与位于耳蜗外毛细胞基部的胆碱能受体具有相似的药理学特性。
