Proliferation of cultured human gingival fibroblasts caused by isradipine, a dihydropyridine-derivative calcium antagonist.
As it was reported earlier that isradipine, a Ca superset 2+ antagonist of dihydropyridine derivative class, caused regression of nifedipine-induced hyperplasia of human gingiva, experiments were performed to examine whether or not isradipine would solely inhibit the proliferation of cultured gingival fibroblasts. Normal human gingival fibroblast Gin-1 cells were used to test the impact of this medication. Fibroblast proliferation in the presence of isradipine (10 microM) was examined by using the reagent water-soluble tetrazolium-1 (WST-1). The level of basic fibroblast growth factor (bFGF) in the cell-free supernatant of each well was determined by using an enzyme-linked immunosorvent assay (ELISA) kit. The production of type I collagen was assayed by ELISA. Isradipine significantly enhanced the cell proliferation from the second day of the culture period. Also, isradipine raised the level of bFGF in the culture medium. The same concentration, also significantly enhanced the production of type I collagen. In conclusion, we were able to prove that isradipine causes the proliferation of cultured gingival fibroblasts as well as other dihydropyridine-derivative Ca superset 2+ antagonists do. In order to prevent the gingival overgrowth, it is advisable to be very careful in the use of isradipine as a therapy for hypertension and other indications.
Hattori
T
T
Department of Dental Pharmacology, Matsumoto Dental University, Shiojiri 399-0781, Japan. hattori@po.mdu.ac.jp
Hirai
K
K
Wang
P
P
Fujimura
S
S
D002118:Calcium / Q000037:antagonists & inhibitors; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D024042:Collagen Type I / Q000096:biosynthesis / Q000187:drug effects; D003470:Culture Media / Q000032:analysis; D004095:Dihydropyridines / Q000737:chemistry / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D017275:Isradipine / Q000737:chemistry / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D024042:Collagen Type I; D003470:Culture Media; D004095:Dihydropyridines; D005346:Fibroblast Growth Factors; C038806:1,4-dihydropyridine; D002118:Calcium; D017275:Isradipine