Pharmacological evidences for the stimulation of calcium-sensing receptors by nifedipine in gingival fibroblasts
Toshimi Hattori1★, Toshiaki Ara1, Yoshiaki Fujinami1★ Corresponding author
- 1Department of Dental Pharmacology, Matsumoto Dental University, Shiojiri 399-0781, Japan.
CORRESPONDENCE
Toshimi Hattori
Department of Dental Pharmacology, Matsumoto Dental University, Shiojiri 399-0781, Japan.
Volume 2, Issue 1 · pp. 30–35 · PUBLISHED 2011 · DOI: 10.4103/0976-500X.77111
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ABSTRACT
Objective: To investigate pharmacologically whether CaSRs are involved in the Ca2+ antagonist-induced [Ca2+]i elevation in gingival fibroblasts. Materials and Methods: Gin-1 cells, normal human gingival fibroblasts, were used as the material. The [Ca2+]i was measured with fura-2/AM, a Ca2+-sensitive fluorescent dye. Results: At first, we confirmed the existence of CaSRs in these cells by showing that [Ca2+]i was elevated by high concentrations of extracellular Ca2+ and by prototypic agonists of the CaSR such as gentamicin. The action of gentamicin was antagonized by inhibitors of phospholipase C (PLC), inositol trisphosphate (IP3) receptors, NSCCs, and, importantly, by the CaSR antagonist, NPS2390. Furthermore, the action of gentamicin was potentiated by activators of PLC and protein kinase C (PKC). This confirmed the pathway components mediating Ca2+ responses to a known agonist of the CaSR. We then investigated whether nifedipine (an L-type Ca2+ channel blocker) stimulates CaSRs to elevate [Ca2+]i via a similar mechanism. Nifedipine Ca2+ responses were dose-dependently blocked by NPS2390 and by the same inhibitors of PLC, IP3 receptors, and NSCCs that disrupted the action of gentamicin. Calphostin C (a PKC inhibitor) and TMB-8 (an inhibitor of Ca2+ release from stores) also inhibited the nifedipine-induced [Ca2+]i elevation. Conclusion: These findings suggest that CaSRs are involved in the nifedipine-induced [Ca2+]i elevation in gingival fibroblasts.
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Hattori, T., Ara, T., & Fujinami, Y. (2011). Pharmacological evidences for the stimulation of calcium-sensing receptors by nifedipine in gingival fibroblasts. Journal of Pharmacology and Pharmacotherapeutics, 2(1), 30–35. https://doi.org/10.4103/0976-500X.77111