Journal of Pharmacology and Pharmacotherapeutics

ORIGINAL PAPER
Year
: 2011  |  Volume : 2  |  Issue : 1  |  Page : 30--35

Pharmacological evidences for the stimulation of calcium-sensing receptors by nifedipine in gingival fibroblasts


Toshimi Hattori, Toshiaki Ara, Yoshiaki Fujinami 
 Department of Dental Pharmacology, Matsumoto Dental University, Shiojiri 399-0781, Japan

Correspondence Address:
Toshimi Hattori
1780 Hirooka-Gohbara, Shiojiri
Japan

Objective: To investigate pharmacologically whether CaSRs are involved in the Ca 2+ antagonist-induced [Ca 2+]i elevation in gingival fibroblasts. Materials and Methods: Gin-1 cells, normal human gingival fibroblasts, were used as the material. The [Ca 2+ ]i was measured with fura-2/AM, a Ca 2+ -sensitive fluorescent dye. Results: At first, we confirmed the existence of CaSRs in these cells by showing that [Ca 2+ ]i was elevated by high concentrations of extracellular Ca 2+ and by prototypic agonists of the CaSR such as gentamicin. The action of gentamicin was antagonized by inhibitors of phospholipase C (PLC), inositol trisphosphate (IP 3 ) 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 Ca 2+ responses to a known agonist of the CaSR. We then investigated whether nifedipine (an L-type Ca 2+ channel blocker) stimulates CaSRs to elevate [Ca 2+ ]i via a similar mechanism. Nifedipine Ca 2+ responses were dose-dependently blocked by NPS2390 and by the same inhibitors of PLC, IP 3 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 [Ca 2+ ]i elevation in gingival fibroblasts.


How to cite this article:
Hattori T, Ara T, Fujinami Y. Pharmacological evidences for the stimulation of calcium-sensing receptors by nifedipine in gingival fibroblasts.J Pharmacol Pharmacother 2011;2:30-35


How to cite this URL:
Hattori T, Ara T, Fujinami Y. Pharmacological evidences for the stimulation of calcium-sensing receptors by nifedipine in gingival fibroblasts. J Pharmacol Pharmacother [serial online] 2011 [cited 2019 Dec 7 ];2:30-35
Available from: http://www.jpharmacol.com/article.asp?issn=0976-500X;year=2011;volume=2;issue=1;spage=30;epage=35;aulast=Hattori;type=0