A Role of Protein Kinase C in the Alteration of Renal Glucose-6-phosphatase Activity Caused by Fluoride

Abstract

In this study, protein kinase C was demonstrated to operate as a down-regulator of glucose-6-phosphatase in the kidney, at least. Renal glucose-6-phosphatase activity reached a maximum level in 3 h after the administration of fluoride to rats. The incremental increase of renal glucose-6-phosphatase activity caused by fluoride administration was markedly amplified by the administration of staurosporine (66 μg/kg, i.p.), which has inhibitory activity against protein kinase C, or by the administration of H-7 (5 μmol/kg, i.p.), a specific and strong inhibitor of protein kinase C. Interestingly, the finding indicated that protein kinase C operates as a down regulator of renal glucose-6-phosphatase activity. The finding was reconfirmed by the result that fluoride-stimulated glucose-6-phosphatase activity was further enhanced by treatment with calphostin C (200 nmol/kg, i.p.), a specific and strong inhibitor of protein kinase C, but the change was small. Moreover, calmodulin was indicated as being possibly concerned with the down regulation of renal glucose-6-phosphatase activity by using W-7 (5μmol/kg, i.p.), a calmodulin specific inhibitor.