Effect of cocaine on the 5-HT₃ receptor-mediated ion current inXenopus oocytes

The cloned 5-HT₃ receptor from NCB-20 neuroblastoma cells was expressed inXenopus oocytes. In these oocytes, 5-HT, the selective 5-HT₃ receptor agonists, 2-methyl-5-HT andm-chlorophenylbiguanide activated an inward current which was sensitive to the specific 5-HT₃ receptor antagonist LY278584. Cocaine (0.1 to 10 μM) reversibly inhibited the current activated by 1 μM 5-HT in a concentration-dependent manner. The IC₅₀ value is 0.7 μM and the apparent Hill coefficient is 1.55. This effect of cocaine was not dependent on membrane potential. Cocaine also produced a parallel shift of the 5-HT concentration-response curve to the right and did not reduce the maximal current induced by 5-HT. In the presence of 3 μM cocaine, the EC₅₀ value of 5-HT was increased from 3.08 μM to 6.1 μM. Other local anesthetics such as tricaine and lidocaine also inhibited the current induced by 5-HT. These results suggest that the 5-HT₃ receptors expressed inXenopus oocytes exhibit properties similar to those in sensory neurons and neuroblastoma cells and were blocked by cocaine in a competitive manner.