ABSTRACT
1 alpha, 25-Dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) has been shown to rapidly increase cytosolic calcium in freshly isolated and cultured rat hepatocytes. The rise in cytosolic calcium is dependent on phospholipase A2 (PLA2) activation and cell alkalinization through the Na+/H+ antiport system. To further characterize the rapid effects of 1 alpha, 25-(OH)2D3, cultured hepatocytes were treated with inhibitors of PLA2 and the Na+/H+ antiport system. 1 alpha, 25-(OH)2D3 treatment caused a 31-66% increase in [32P]lysophosphatidylinositol (LPI) and a 0.04 increase in pH within 5 minutes. Inhibition of the Na+/H+ antiport system with amiloride or removal of extracellular sodium abolished the 1 alpha, 25-(OH)2D3 rise in LPI. Inhibition of PLA2 with bromophenacylbromide also blocked the 1 alpha, 25-(OH)2D3-induced rise in [32P]LPI and cytosolic alkalinization in response to 1 alpha, 25-(OH)2D3. The data indicate that 1 alpha, 25-(OH)2D3 rapidly increases the activity of PLA2 and the Na+/H+ antiport system. The production of LPI is dependent on PLA2 activation and cell alkalinization through the Na+/H+ antiport system. It appears that the two events are interdependent in hepatocytes.
Subject(s)
Calcitriol/pharmacology , Calcium/metabolism , Liver/metabolism , Phospholipases A/metabolism , Sodium-Hydrogen Exchangers/metabolism , Acetophenones/pharmacology , Amiloride/pharmacology , Animals , Cells, Cultured , Cytosol/drug effects , Cytosol/metabolism , Enzyme Activation/drug effects , Liver/drug effects , Lysophospholipids/metabolism , Phospholipases A/antagonists & inhibitors , Phospholipases A2 , Rats , Sodium/physiology , Sodium-Hydrogen Exchangers/antagonists & inhibitorsABSTRACT
The effect of exercise on bone mass is unclear. To determine the skeletal effect of weight-bearing exercise in premenopausal women, we prospectively evaluated the effects of a weight-training program on lumbar spine bone mass in 10 women (mean +/- SEM, 36.2 +/- 1.3 yr) and compared the results with those in 7 sedentary women (40.4 +/- 1.6 yr). None of the women had previously participated in a weight-training program, and all ingested a 500-mg calcium supplement each day throughout the study. Axial loading and balance of large muscle groups were emphasized. Individual strength increased by 57 +/- 8% over 9 months. Despite the increase in muscle strength, lumbar spine bone density in the exercising women decreased by 2.90% at 4.5 months and 3.96% at 9 months (P = 0.01). In contrast, there was no change in lumbar density in the controls over the 9-month period. We conclude that short term weight training at this frequency and intensity decreases vertebral bone mass in premenopausal women.
