Comparative study of calcium-channel blockers on cell proliferation, DNA and collagen syntheses, and EGF receptors of cultured gingival fibroblasts derived from human nifedipine, nicardipine and nisoldipine responders.
Our previous study indicated that fibroblasts derived from patients reactive to nifedipine might be susceptible to the other calcium-channel blockers (nicardipine, verapamil and diltiazem) in terms of cell proliferation, DNA synthesis, and collagen synthesis. Thus, the present investigation was designed to clarify the cross-reactivity among dihydropyridine calcium-channel blockers (nifedipine, nicardipine, and nisoldipine). Human gingival fibroblasts derived from seven, two, and one patients who developed gingival overgrowth as a result of nifedipine, nicardipine, and nisoldipine medications, respectively, were examined in terms of the effect of calcium-channel blockers (nifedipine, diltiazem, verapamil, and nicardipine) on cell proliferation, DNA synthesis, collagen synthesis, and the number of epidermal growth factor (EGF) receptors. Phenytoin was used as a positive control. With most of the calcium-channel blockers and phenytoin, fibroblasts from patients reactive to nifedipine and nicardipine medications gave a better cell proliferation rate, DNA synthesis, and an increased number of EGF receptors, compared to non-drug-treated control. However, this was not the case for calcium-channel blockers tested in fibroblasts from patients reactive to nisoldipine medication.
Matsumoto
H
H
Department of Pharmacology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Noji
I
I
Akimoto
Y
Y
Fujii
A
A
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D005434:Flow Cytometry; D005881:Gingiva / Q000187:drug effects* / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009529:Nicardipine / Q000009:adverse effects* / Q000494:pharmacology; D009543:Nifedipine / Q000009:adverse effects* / Q000494:pharmacology; D015737:Nisoldipine / Q000009:adverse effects*; D010672:Phenytoin / Q000494:pharmacology; D019275:Radiopharmaceuticals; D013223:Statistics as Topic; D014316:Tritium; D014700:Verapamil / Q000494:pharmacology
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D019275:Radiopharmaceuticals; D014316:Tritium; D015737:Nisoldipine; D010672:Phenytoin; D003094:Collagen; D004247:DNA; D014700:Verapamil; D009529:Nicardipine; D066246:ErbB Receptors; D004110:Diltiazem; D009543:Nifedipine