Abstract

We investigated the effect of phencyclidine (PCP) on the voltage-dependent K+ current in whole cell recordings from murine thymocytes. PCP caused a dramatic, reversible and dose-dependent decrease of the current. An analysis of the dose-response relationship suggests a single site of action for PCP with an IC50 of 4.7 microM. Dextrorphan and naloxone also inhibited the current, although their effects were of a lower magnitude than those of PCP. Neither 10 microM dextrorphan nor 100 microM naloxone antagonized the inhibitory action of 10 microM PCP. The analysis of the dose-response curve for PCP in presence of 100 microM naloxone suggested that the two drugs act at the same site. We also investigated the effect of morphine on the K+ current. Morphine, in concentrations up to 100 microM, inhibited the K+ current less than dextrorphan or PCP. The kinetics and voltage dependence of the currents in the presence of morphine suggest that it interacts with a different site or different conformation of the channel than the other three compounds. Our findings show that certain opioids can act on thymocytes through a system completely different from the typical opioid receptors.