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Pharmacological Evidence for the Involvement of Calcium Entry through TRPV1 Channels in Nifedipine-Induced [Ca2+]i Elevation in Gingival Fibroblasts

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DOI: 10.4236/pp.2012.34057    4,355 Downloads   6,968 Views  

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’.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

T. Hattori, T. Ara and Y. Fujinami, "Pharmacological Evidence for the Involvement of Calcium Entry through TRPV1 Channels in Nifedipine-Induced [Ca2+]i Elevation in Gingival Fibroblasts," Pharmacology & Pharmacy, Vol. 3 No. 4, 2012, pp. 427-432. doi: 10.4236/pp.2012.34057.

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