Inhibition by SK&F 96365 of Ca2+ current, IL-2 production and activation in T lymphocytes

Br J Pharmacol. 1994 Nov;113(3):861-8. doi: 10.1111/j.1476-5381.1994.tb17072.x.

Abstract

1. By use of whole cell patch-clamp and Indo-1 fluorescence studies of the Jurkat T leukaemic cell line, we show that the new organic antagonist of receptor-mediated Ca2+ entry, SK&F 96365, inhibits the T cell Ca2+ current in a dose-dependent fashion, with an IC50 of 12 microM. 2. SK&F 96365 also inhibits [3H]-thymidine incorporation and interleukin-2 (IL-2) synthesis in peripheral blood lymphocytes. 3. SK&F 96365 has no effect on Ca2+ stores release or K+ channels. 4. This is the first account of an organic inhibitor of the T cell Ca2+ current. The ability of SK&F 96365 to inhibit IL-2 synthesis and cell proliferation suggests that a new class of related Ca2+ channel blockers can be developed as immunosuppressive agents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects*
  • Cell Division / drug effects
  • Humans
  • Imidazoles / pharmacology*
  • Immunosuppressive Agents / pharmacology
  • Interleukin-2 / biosynthesis*
  • Lymphocyte Activation / drug effects*
  • Potassium Channels / drug effects
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Tumor Cells, Cultured

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Imidazoles
  • Immunosuppressive Agents
  • Interleukin-2
  • Potassium Channels
  • 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
  • Calcium