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.
Kunert-Radek
J
J
Institute of Endocrinology, Medical Academy of Lodz, Poland.
Stepien
H
H
Lyson
K
K
Pawlikowski
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009553:Nimodipine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D013154:Spleen / Q000166:cytology*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D011725:Pyridines; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C040525:CGP 28392; D004247:DNA; D002122:Calcium Chloride