A role of protein kinase C in the alteration of renal glucose-6-phosphatase activity caused by fluoride.
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 micrograms/kg, i.p.), which has inhibitory activity against protein kinase C, or by the administration of H-7 (5 mumol/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 (5 mumol/kg, i.p.), a calmodulin specific inhibitor.
Suketa
Y
Y
Department of Environmental Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, Japan.
Ibuki
Y
Y
Imagawa
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000262:Adenylyl Cyclases / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005459:Fluorides / Q000494:pharmacology*; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine
D000470:Alkaloids; D007546:Isoquinolines; D009281:Naphthalenes; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D005952:Glucose-6-Phosphatase; D000262:Adenylyl Cyclases; D019311:Staurosporine; C058819:calphostin C; D005459:Fluorides