Effects of calcium channel modulators on the proliferation of mouse spleen lymphocytes in vitro

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 studied in 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 x 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 x 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 x 10(-3) M calcium chloride. These findings indicate that calcium channel modulators can regulate the proliferation of mouse spleen lymphocytes in vitro.