In vivo and in vitro study of the effects of chlorpromazine on tooth mineralization in rats and mice.
The effects of chlorpromazine (CPZ) on tooth mineralization were examined using incisor dentine in adult rats and cultured tooth germs of mandibular first molars dissected from mouse embryos. CPZ (10, 50 and 250 mg/kg, s.c.) substantially inhibited dentine mineralization as evaluated by contact microradiographs. Plasma calcium and phosphorus concentrations were not decreased by CPZ (10 and 50 mg/kg). Physicochemical effects were not involved in the action of CPZ on the mineralization. In vitro experiments showed that CPZ (1 and 10 microM) inhibited mineralization and alkaline phosphatase (ALP) activity in the tooth germs. As CPZ has the properties of a calmodulin antagonist, the calmodulin antagonists W-7 and W-5 were also examined. Both inhibited mineralization and ALP activity in tooth germs; W-5 had less effect than W-7. These in vivo and in vitro findings suggest that CPZ inhibited cell-mediated mineralization in dentine without affecting the calcium-regulating system and physicochemical mineral deposition. In addition, calmodulin could be involved in cell-mediated mineralization.
Togari
A
A
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
Kondo
M
M
Arai
M
M
Matsumoto
S
S
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000097:blood; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology; D002746:Chlorpromazine / Q000633:toxicity*; D003804:Dentin / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010710:Phosphates / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014074:Tooth Calcification / Q000187:drug effects*; D014083:Tooth Germ / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D002147:Calmodulin; D010710:Phosphates; D000469:Alkaline Phosphatase; D002118:Calcium; D002746:Chlorpromazine