Verbitsky M, Rothlin C V, Katz E, Elgoyhen A B
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Vuelta de Obligado 2490, 1428, Buenos Aires, Argentina.
Neuropharmacology. 2000 Oct;39(13):2515-24. doi: 10.1016/s0028-3908(00)00124-6.
The rat alpha9 nicotinic acetylcholine receptor (nAChR) was expressed in Xenopus laevis oocytes and tested for its sensitivity to a wide variety of cholinergic compounds. Acetylcholine (ACh), carbachol, choline and methylcarbachol elicited agonist-evoked currents, giving maximal or near maximal responses. Both the nicotinic agonist suberyldicholine as well as the muscarinic agonists McN-A-343 and methylfurtrethonium behaved as weak partial agonists of the receptor. Most classical cholinergic compounds tested, being either nicotinic (nicotine, epibatidine, cytisine, methyllycaconitine, mecamylamine, dihydro-beta-erythroidine), or muscarinic (muscarine, atropine, gallamine, pilocarpine, bethanechol) agonists and antagonists, blocked the recombinant alpha9 receptor. Block by nicotine, epibatidine, cytisine, methyllycaconitine and atropine was overcome at high ACh concentrations, suggesting a competitive type of block. The present results indicate that alpha9 displays mixed nicotinic-muscarinic features that resemble the ones described for the cholinergic receptor of cochlear outer hair cells (OHCs). We suggest that alpha9 contains the structural determinants responsible for the pharmacological properties of the native receptor.
大鼠α9烟碱型乙酰胆碱受体（nAChR）在非洲爪蟾卵母细胞中表达，并测试其对多种胆碱能化合物的敏感性。乙酰胆碱（ACh）、卡巴胆碱、胆碱和甲基卡巴胆碱引发激动剂诱发电流，产生最大或接近最大反应。烟碱型激动剂辛二酰胆碱以及毒蕈碱型激动剂 McN-A-343 和甲基呋罗氨甲酰胆碱均表现为该受体的弱部分激动剂。所测试的大多数经典胆碱能化合物，无论是烟碱型（尼古丁、依博加碱、金雀花碱、甲基乌头碱、美加明、二氢β-刺桐啶）还是毒蕈碱型（毒蕈碱、阿托品、加拉明、毛果芸香碱、氨甲酰甲胆碱）激动剂和拮抗剂，均能阻断重组α9受体。在高ACh浓度下，尼古丁、依博加碱、金雀花碱、甲基乌头碱和阿托品的阻断作用被克服，表明为竞争性阻断类型。目前的结果表明，α9表现出混合的烟碱型-毒蕈碱型特征，类似于耳蜗外毛细胞（OHCs）胆碱能受体所描述的特征。我们认为，α9包含负责天然受体药理学特性的结构决定因素。
