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

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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.