Calcitonin stimulates adenosine-5'-triphosphate synthesis calcium-dependently in the hepatic mitochondria of rats.

Abstract

The effect of calcitonin (CT) on adenosine-5'-triphosphate (ATP) synthesis in the hepatic mitochondria of rats was investigated. Administration of CT (80 MRC mU/100 g body weight) produced a marked elevation of ATP content in the hepatic cytosol. This increase was completely inhibited by administration of 2, 4-dinitrophenol (0.1 mg/100 g), an inhibitor of oxidative phosphorylation of mitochondria. Verapamil (1.0 mg/100 g) also inhibited the hormonal effect on hepatic ATP content. Moreover, administration of calcium chloride (2.0 and 4.0 mg Ca2+/100 g) elevated the cytosolic ATP content by about 1.8-and 2.3-fold, respectively. Meanwhile, administration of CT produced a remarkable increase of ATPase activity in the hepatic mitochondria. Calcium contents in both the liver and the mitochondria were raised by CT administration. The removal of the mitochondrial calcium by washing with 10 mM ethyleneglycol-bis (2-aminoethylether) -N, N, N', N'-tetraacetic acid (EGTA, pH 7.4) caused complete loss of the increase in mitochondrial adenosine triphosphatase (ATPase) activity induced by CT administration. The CT-increased ATPase activity was appreciably increased by addition of 10 and 50 μM Ca2+, but this increase was not altered by addition of 10 μM trifluoperazine or calmodulin (2.5 μg/ml). These results suggest that CT stimulates ATP synthesis in the hepatic mitochondria, and that the hormonal effect may be mediated through calcium, but not calmodulin.