Phencyclidine blocks voltage-dependent potassium currents in murine thymocytes.
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.
Fiorica-Howells
E
E
Neurosciences Department, Roche Institute of Molecular Biology, Nutley, New Jersey.
Gambale
F
F
Horn
R
R
Osses
L
L
Spector
S
S
D000818:Animals; D003917:Dextrorphan / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D015221:Potassium Channels; D003917:Dextrorphan; D009270:Naloxone; D009020:Morphine; D010622:Phencyclidine