Calcium antagonist isradipine-induced calcium influx through nonselective cation channels in human gingival fibroblasts.
Isradipine raises the cytosolic Ca2+ concentration ([Ca2+]i) in human gingival fibroblasts by enhancing Ca2+ influx through the plasma membrane. To research the pathways through which Ca2+ enters the cells, we examined the interactive effects of isradipine and blockers or enhancers of nonselective cation channels (NSCCs) and Na+/Ca2+ exchangers (NCXs). Normal human gingival fibroblast Gin-1 cells were used. The [Ca2+]i was measured with the Ca2+-sensitive fluorescent dye fura-2/AM. Changes in the fluorescence intensity of fura-2 in the cells were recorded with a video-imaging analysis system. Ca2+ antagonists (nifedipine, verapamil, and diltiazem in the concentration range of 1 to 20 microM) other than isradipine also raised the [Ca2+]i. All of the NSCC inhibitors (SK&F 96365, GdCl3, HgCl2 and flufenamic acid), but none of the NCX inhibitors (KB-R 7943 and benzamil), significantly decreased the [Ca2+]i raised by isradipine (3 microM). Neither the Na+ ionophore monensin nor Na+/K+ ATPase inhibitor ouabain had any significant effect on the isradipine-induced [Ca2+]i rise. Taken together, our data indicate that Ca2+ entry through the NSCCs is involved in the isradipine-induced [Ca2+]i rise. The results obtained here play an important role in the development of drugs for etiologic therapy of gingival overgrowth.
Hattori
T
T
Department of Dental Pharmacology, Matsumoto Dental University, Shiojiri, Japan. hattori@po.mdu.ac.jp
Wang
P L
PL
D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019214:Gingival Overgrowth / Q000209:etiology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism*; D017275:Isradipine / Q000009:adverse effects / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D007473:Ion Channels; C049925:fura-2-am; D016257:Fura-2; D017275:Isradipine