Dual regulation of alkaline phosphatase activity by calcitonin in porcine kidney cells.
Intracellular signal transduction for regulation of alkaline phosphatase (ALP) activity in renal epithelial cells treated with calcitonin is not yet completely understood, although it is known that calcitonin receptors couple to cyclic AMP-dependent protein kinase (PKA) and calcium/phospholipid-dependent protein kinase (PKC). Salmon calcitonin increased the cyclic AMP content in LLC-PK1 porcine kidney cells in a concentration-dependent manner. When the confluent cells were incubated for 47 h after a 1 h-pulse exposure or continuously exposed to calcitonin and forskolin for 48 h, ALP activity in the cells was increased by calcitonin about 2-fold compared with the basal activity at the maximum level but was not dependent on the exposure time; it was markedly increased by forskolin in parallel with the exposure time. The increase in activity produced by calcitonin was abolished by a PKA inhibitor H-89, and, in contrast, potentiated by a PKC inhibitor, NA-382 to near the forskolin-induced level. These results indicate that calcitonin exerts a dual-regulation of ALP activity in LLC-PK1 cells, positively through the PKA pathway and negatively through PKC.
Miyamoto
K
K
Department of Pharmacology and Pharmaceutics, Graduate School of Natural Science and Technology, Kanazawa University, Japan.
Horita
T
T
Waki
Y
Y
Suzuki
R
R
Yamamoto
S
S
Moritani
S
S
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D018374:LLC-PK1 Cells; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000031:analogs & derivatives; D013552:Swine
D000470:Alkaloids; D004791:Enzyme Inhibitors; C075317:N-ethoxycarbonyl-7-oxostaurosporine; D002116:Calcitonin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000469:Alkaline Phosphatase; D019311:Staurosporine