Effect of cocaine on the 5-HT3 receptor-mediated ion current in Xenopus oocytes.
The cloned 5-HT3 receptor from NCB-20 neuroblastoma cells was expressed in Xenopus oocytes. In these oocytes, 5-HT, the selective 5-HT3 receptor agonists, 2-methyl-5-HT and m-chlorophenylbiguanide activated an inward current which was sensitive to the specific 5-HT3 receptor antagonist LY278584. Cocaine (0.1 to 10 microM) reversibly inhibited the current activated by 1 microM 5-HT in a concentration-dependent manner. The IC50 value is 0.7 microM 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 microM cocaine, the EC50 value of 5-HT was increased from 3.08 microM to 6.1 microM. 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 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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Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
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Zhang
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D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D017136:Ion Transport / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D014982:Xenopus laevis
D011985:Receptors, Serotonin; D012701:Serotonin; D008012:Lidocaine; D003042:Cocaine