Fan P, Visentin S, Weight F F
Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
J Pharmacol Exp Ther. 1994 Oct;271(1):262-6.
Application of 5-hydroxytryptamine (5-HT) to freshly isolated rat nodose ganglion neurons produced a fast inward current when measured using the whole-cell patch-clamp technique. This current was blocked by the 5-HT3 receptor antagonist MDL72222. The selective 5-HT3 receptor agonist 2-methyl-5-HT induced a similar current. Cocaine (0.1-300 microM) applied simultaneously with 5-HT (0.25-50 microM) inhibited the 5-HT-induced current. The inhibition did not appear to be voltage dependent. If cocaine was preapplied for about 30 sec, the effect of cocaine on 5-HT current was increased. Both the peak and the steady-state 5-HT current was depressed by cocaine. However, the peak current was more sensitive to cocaine than the steady-state current. The concentration-response curves of cocaine in different agonist concentrations revealed that cocaine competitively inhibited the 5-HT3 receptor-mediated current with a pA2 value of 5.8 and an apparent KD of 1.6 microM. These results suggest that in addition to the other well known mechanisms, the 5-HT3 receptor-ion channel complex is another site for cocaine action.
当使用全细胞膜片钳技术进行测量时，将5-羟色胺（5-HT）应用于新鲜分离的大鼠结状神经节神经元会产生快速内向电流。该电流被5-HT3受体拮抗剂MDL72222阻断。选择性5-HT3受体激动剂2-甲基-5-HT诱导出类似的电流。与5-HT（0.25 - 50 microM）同时应用的可卡因（0.1 - 300 microM）抑制了5-HT诱导的电流。这种抑制似乎不依赖于电压。如果预先应用可卡因约30秒，可卡因对5-HT电流的作用会增强。可卡因使5-HT电流的峰值和稳态值均降低。然而，峰值电流比稳态电流对可卡因更敏感。不同激动剂浓度下可卡因的浓度-反应曲线表明，可卡因以pA2值为5.8和表观KD为1.6 microM竞争性抑制5-HT3受体介导的电流。这些结果表明，除了其他众所周知的机制外，5-HT3受体-离子通道复合物是可卡因作用的另一个位点。
