Rat ileal alkaline phosphatase activity and secretion is stimulated by alterations in calcium metabolism.
The mechanism of calmodulin-stimulated alkaline phosphatase activity was studied in the rat. In calmodulin-treated rats (2.5 micrograms/animal, intraperitoneally) alkaline phosphatase (ALP) activity was elevated 11-fold in the ileum, 1.5-fold in the duodenum and calvarium, 3-fold in serum, and not at all in liver. The elevated ALP activity was prevented by prior treatment with flunarizine, a calcium channel blocker, and by W-7, a calmodulin antagonist. cAMP content in ileum paralleled the timing and changes in ALP activity, but was not elevated in the duodenum or calvarium. Calcium ionophore A23187 and calcitonin treatment also increased ileal, duodenal, and calvarial ALP activity, but by less than the response to calmodulin. All of these treatments caused a 2-fold elevation in serum 1,25-dihydroxyvitamin D-3 (1,25(OH)2D3) levels. Pretreatment of the animals with parathyroid hormone prevented the rise of both ALP activity and of 1,25(OH)2D3. Administration of 1,25(OH)2D3 alone stimulated a different pattern of increased ALP activity, greater in duodenum than ileum. The uptake of 45Ca by calmodulin was also elevated in ileum and calvarium. These data suggest that shifts in calcium movement, perhaps mediated by vitamin D, can alter ALP activity, and may provide a mechanism for rapid control of the secretion of this enzyme.
Komoda
T
T
Department of Biochemistry, Saitama Medical School, Japan.
Koyama
I
I
Arai
Y
Y
Sekine
T
T
Sakagishi
Y
Y
Kumegawa
M
M
Alpers
D H
DH
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005444:Flunarizine / Q000494:pharmacology; D007082:Ileum / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002147:Calmodulin; D007527:Isoenzymes; D010281:Parathyroid Hormone; D002116:Calcitonin; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D002117:Calcitriol; D005444:Flunarizine; D002118:Calcium