Effects of calcium channel modulators on the proliferation of mouse spleen lymphocytesin vitro

Abstract

The effects of nimodipine (voltage-dependent calcium channel blocker), CGP 28392 and BAY K 8644 (novel dihydropyridine derivatives that are considered as calcium entry stimulators) on the spontaneous proliferation of mouse spleen lymphocytes were studiedin vitro. [³H]-thymidine incorporation into DNA of lymphocytes was used as an sensitive index of the cell proliferation. It has been found that nimodipine (10⁻⁴ M–10⁻⁶ M) significantly inhibited the [³H]-thymidine uptake in a dose dependent fashion with ED₅₀ value of 2.4×10⁻⁵ M. Unexpectedly, CGP 28392 (10⁻⁴ M–10⁻⁷ M) acts as a calcium entry blocker and produces a strong inhibitory effect on lymphocyte proliferation (ED₅₀−2×10⁻⁵ M). BAY K 8644 at a high concentration (10⁻⁴ M) also has an inhibitory effect but at a lower concentration (10⁻⁶ M–10⁻¹⁰ M) significantly increased [³H]-thymidine uptake and abolished the inhibitory effect of nimodipine. This effect of nimodipine was also reversed by 5×10⁻³ M calcium chloride. These findings indicate that calcium channel modulators can regulate the proliferation of mouse spleen lymphocytesin vitro.