The effect of acivicin, an inhibitor of gamma-glutamyl transpeptidase on mouse molar development in vitro.

Abstract

Gamma-glutamyl transpeptidase (GGT) is a membrane-bound enzyme found on the surface of cells having secretory or resorptive functions. GGT has been found to be strongly localized in the stellate reticulum of the developing tooth. It has been proposed that the role for GGT in tooth development is related to the transport of amino acids into the cell via the gamma-glutamyl cycle. In order to ascribe a role for GGT and the stellate reticulum in the developing tooth, the activity of GGT was inhibited by a daily 1 hour application of the glutamine analog, acivicin (Upjohn), to mouse first molar tooth germs in serum free organ culture for periods of 5 to 8 days. Acivicin treatment effectively arrested tooth development. Additionally, tooth germs were allowed to recover for 4 to 7 days following a 4 day treatment with acivicin or they were incubated in media supplemented with additional glutamine or nucleosides during the acivicin treatment. Tooth germs were able to recover when returned to control medium. However, treated teeth were smaller in size than the controls. Glutamine partially compensated for the acivicin treatment. Nucleotide supplemented media appeared to almost completely override the inhibitory effect of acivicin. It appears that the inhibition by acivicin is primarily due to its effect on DNA and RNA synthesis. The inhibition of the gamma-glutamyl cycle by acivicin was unaffected by the addition of glutamine or nucleosides. Therefore, inhibition of the gamma-glutamyl cycle and GGT does not seem to significantly affect the development of teeth at the stages studied.