Abstract
Background: Among anti-hypertension drugs, calcium (Ca2+) antagonists cause gingival overgrowth as a side effect. We previously discovered that this side effect was due to elevation of the calcium concentration in the cytosol ([Ca2+]i). Ca2+ entry through non-selective cation channels (NSCCs) and Ca2+ release from intracellular Ca2+ stores are involved in this [Ca2+]i elevation. Furthermore, we discovered that calcium-sensing receptors (CaSRs) participate in nifedipine-induced [Ca2+]i elevation. Transient receptor potential (TRP) channels have been identified as NSCCs. In the present study, we undertook experiments to determine if TRPV1 channels are present in gingival fibroblasts and to ascertain if nifedipine-activated NSCCs are TRPV1 channels. Methods Normal human gingival fibroblast Gin-1 cells were used. The [Ca2+]i was measured using a video-imaging analysis system with the Ca2+-sensitive fluorescent dye fura-2/AM. Results: The NSCC inhibitor SKF96365 significantly inhibited nifedipine-induced [Ca2+]i elevation. TRPV1 channel agonists such as capsaicin, olvanil and resiniferatoxin concentration-dependently elevated the [Ca2+]i. The TRPV1 channel activator anandamide concentration-dependently increased the [Ca2+]i. The TRPV1 channel antagonists capsazepine, AMG9810, iodoresiniferatoxin, ruthenium red, and SB366791 significantly inhibited nifedipine-induced [Ca2+]i elevation. Conclusion: These results suggest that Ca2+ entry through TRPV1 channels is involved in the nifedipine-induced [Ca2+]i elevation seen in gingival fibroblasts. We describe here a modified version of our ‘calcium trigger theory’.
Highlights
Among calcium (Ca2+) antagonists, anti-hypertension drugs cause gingival overgrowth as a side effect [1]
The TRPV1 channel antagonists capsazepine, AMG9810, iodoresiniferatoxin, ruthenium red, and SB366791 significantly inhibited nifedipine-induced [Ca2+]i elevation. These results suggest that Ca2+ entry through TRPV1 channels is involved in the nifedipine-induced [Ca2+]i elevation seen in gingival fibroblasts
The effects of agonists of TRPV1 channels on the [Ca2+]i were examined to confirm the existence of TRPV1 channels in gingival fibroblasts
Summary
Among calcium (Ca2+) antagonists, anti-hypertension drugs cause gingival overgrowth as a side effect [1]. We previously discovered that this side effect is due to elevation of the calcium concentration in the cytosol ([Ca2+]i) and advocated the “calcium trigger theory” as the developing mechanism [2]. This theory was based on results showing that Ca2+ antagonists enhance Ca2+ entry through nonselective cation channels (NSCCs) [3] and Ca2+ release from the intracellular Ca2+ stores (endoplasmic reticula) [4]. We discovered that calcium-sensing receptors (CaSRs) participate in nifedipine (typical Ca2+ antagonist)-induced [Ca2+]i elevation. Conclusion: These results suggest that Ca2+ entry through TRPV1 channels is involved in the nifedipine-induced [Ca2+]i elevation seen in gingival fibroblasts. We describe here a modified version of our “calcium trigger theory”
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