The effects of calcium channel blockers on nuclear factor kappa B activation in the mesangium cells

It has been reported that calcium channel blockers (CCBs) have an inhibitor y action on cell growth and transcriptional changes induced by cytokines an d hormones, In this study, we examined the effects of CCBs on nuclear facto r kappa B (NF kappa B), which plays a key role in the intracellular signali ng of various growth factors and cytokines. The activity of NF kappa B was determined by luciferase assay with the transfection of the reporter gene, which has six NF kappa B-recognizing sequences in the upstream of herpes si mplex Virus thymidine kinase promoter, In cultured human mesangial cells, i ncreased intracellular calcium concentration by calcium ionophore, A23187, showed a stimulatory effect on the phorbor 12-myristate 18-acetate (PMA)-in duced activation of NF kappa B, while L-type calcium channel agonist, Bay K 8644, did not have any significant effects on either basal or PMA-stimulat ed activity of NF kappa B, At a higher concentration (10 mu M), nifedipine, verapamil, or efonidipine showed an inhibitory effect on the activation of NF kappa B by PMA and A23187, while at a lower concentration (1 mu M), onl y efonidipine showed a significant inhibitory effect. From these results, w e conclude that CCBs have an inhibitory effect on NF kappa B via the indepe ndent pathway of an L-type calcium channel and that the potency of this eff ect is variable among L-type calcium channel blockers.