title: Suppressive effects of nonsteroidal anti-inflammatory drugs diclofenac sodium, salicylate and indomethacin on delayed rectifier K+-channel currents in murine thymocytes.
abstract: Lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes, and the channels play crucial roles in the lymphocyte activation and proliferation. Since nonsteroidal anti-inflammatory drugs (NSAIDs), the most commonly used analgesic and antipyretic drugs, exert immunomodulatory effects, they would affect the channel currents in lymphocytes. In the present study, employing the standard patch-clamp whole-cell recording technique, we examined the effects of diclofenac sodium, salicylate and indomethacin on the channel currents in murine thymocytes and the membrane capacitance. Diclofenac sodium and salicylate significantly suppressed the pulse-end currents of the channel. However, indomethacin suppressed both the peak and the pulse-end currents with a significant increase in the membrane capacitance. This study demonstrated for the first time that NSAIDs, such as diclofenac sodium, salicylate and indomethacin, exert inhibitory effects on thymocyte Kv1.3-channel currents. The slow inactivation pattern induced by indomethacin was thought to be associated with microscopic changes in the plasma membrane surface detected by the increase in the membrane capacitance.
authors.affiliation: Department of Physiology I, Tohoku University Graduate School of Medicine, Seiryo-cho, Aoba-ku, Sendai, Miyagi, Japan. kazaitsu@med.tohoku.ac.jp
authors.forename: Itsuro
authors.initials: I
authors.lastname: Kazama
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Murata
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D012980:Sodium Salicylate / Q000494:pharmacology*; D060168:Thymocytes / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051664:Kv1.3 Potassium Channel; D004008:Diclofenac; D012980:Sodium Salicylate; D007213:Indomethacin