Studies of alkaline phosphatase inhibition by p-bromotetramisole in non-mineralizing and mineralizing neonatal hamster tooth germs in vitro.
The effects of l and d-, p-bromotetramisole (pBTM) on alkaline phosphatase were studied in relation to 45Ca2+, 32phosphate and 3H-thymidine uptakes in non-mineralizing second (M2) and mineralizing first (M1) maxillary hamster molar tooth germs under the conditions of organ culture. At the concentration used in culture (10(-3)M), l-pBTM completely inhibited alkaline phosphatase activity in tooth germ homogenates. About 30% of the enzyme activity was inhibited by d-pBTM at the same concentration. In culture, there were no significant differences between the effects of l and d-pBTM isomers on all the parameters measured. In the non-mineralized M2 molars, l and d-pBTM significantly reduced both TCA-soluble and TCA-insoluble 32phosphate uptakes but not 45Ca2+. However, 3H-thymidine uptake was also significantly decreased. In M1 molars, the pBTM isomers significantly reduced the uptake of TCA-soluble 32phosphate and 45Ca2+ but not TCA-insoluble 32phosphate. Ouabain, a specific inhibitor of Na+-K+-ATPase (but not alkaline phosphatase), also significantly reduced 3H-thymidine uptake to the same extent as the pBTM isomers in the non-mineralizing M2 molars, but it did not significantly affect either 32phosphate (TCA-soluble and TCA-insoluble) or 45Ca2+ uptake. Although this inhibitor significantly reduced both 45Ca2+ and TCA-soluble 32phosphate uptake in the mineralizing M1 molars, this effect was much less dramatic than was the case with the pBTM isomers. The reduced 45Ca2+ uptake in the M1 molars is probably a consequence of reduced mineralization since in the non-mineralizing M2 molars calcium uptake was not significantly affected by the pBTM isomers.(ABSTRACT TRUNCATED AT 250 WORDS)
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D002455:Cell Division; D006224:Cricetinae; D008647:Mesocricetus; D009924:Organ Culture Techniques; D010710:Phosphates / Q000378:metabolism; D013773:Tetramisole / Q000031:analogs & derivatives* / Q000494:pharmacology; D014074:Tooth Calcification; D014083:Tooth Germ / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism
D000871:Anthelmintics; D010710:Phosphates; C006226:4-bromotetramisole; D013773:Tetramisole; D000469:Alkaline Phosphatase