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Abstract
The cloned 5-HT 3 receptor from NCB-20 neuroblastoma cells was expressed in Xenopus oocytes. In these oocytes, 5-HT, the selective 5-HT 3 receptor agonists, 2-methyl-5-HT and m-chlorophenylbiguanide activated an inward current which was sensitive to the specific 5-HT 3 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 IC 50 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 EC 50 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-HT 3 receptors expressed in Xenopus oocytes exhibit properties similar to those in sensory neurons and neuroblastoma cells and were blocked by cocaine in a competitive manner.
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