A study of the action of calcitonin by its effects on lead-induced hypercalcemia

Abstract

Summary. Intravenous (i.v.) injection of lead acetate produces an immediate elevation in total plasma calcium and phosphate levels. This is due to the formation of calcium-phosphate compounds which can be removed by centrifugation at 25,000 • g. For this study, the effect of salmon calcitonin (CT) on these lead-induced plasma changes was studied. Intact male rats (175-250 g) were injected i.v. with lead acetate 10-30 mg/kg. Sodium acetateinjected rats served as controls. CT (0.1-0.2 mU/g) injected 30 min prior to lead modified the lead-induced plasma changes as follows: The concentration of lead remaining in plasma was statistically reduced. This was accompanied by a decrease in the amount of colloidal calcium-phosphate removed by ultracentrifugation and a corresponding decrease in the lead-induced elevation of total plasma calcium and phosphate levels. This action of CT was still effective in acutely nephrectomized rats. However, a 15-day pretreatment with a diphosphonate (20 mg EHDP/kg/day) abolished the hypocalcemic effect of CT and also abolished the ability of CT to affect the lead-induced plasma changes. Finally, CT was ineffective if injected in as short a time period as 30 min after lead injection.It is concluded from these studies that CT causes a rapid sequestering of lead from plasma into specific sites in bone. Previous reports show that within minutes after injection, CT causes the formation of calcium-phosphate complexes in fluid at the surfaces of bone and in osteocyte lacunae. It is postulated that lead reacts with these colloids (complexes) in a manner similar to its attachment to calcium and phosphate in plasma, thereby removing this lead from blood.Send qffprint requests to Dr. Roy V. Talmage at the above address.

Reduction of lead-induced hypercalcemia by calcitonin: Comparison between thyroid-intact and thyroidectomized rats

“…These data extend the results recently reported [1] demonstrating that calcitonin has the unique property of reducing the degree of lead-induced hypercalcemia and hyperphosphatemia. The time required for calcitonin to exert this effect is minimal since the maximum response occurs by 1 h. Its du- ration after a single injection of hormone appears to be as short as its hypocalcemic effect.…”

“…It is this postprandial difference that needs explanation. Normally, plasma calcium values in rats fall following feeding [1]. However, due to the extended use of these rats in urine collection experiments, they had become accustomed to consuming the entire day's food allotment within 1 h. Under this situation, plasma calcium concentrations fell only briefly and were rising at 3 h postprandially, this is the only experimental situation in which we have been able to demonstrate any antihypercalcemic effect of CT following ingestion of a meal in which the calcium was not in a readily soluble form.…”

“…The first series of experiments was an extension of our previous study [1]. Lead acetate (20 It is apparent that the maximum suppression of the hypercalcemic response to lead occurred in rats in which CT injection was only 7 rain prior to lead administration (hypercalcemia measured 1 h later).…”

“…The diphosphonate, sodium ethane-l, hydroxyl-l, 1-diphosphonic acid (EHDP), has been shown to abolish the hypocalcemic effect of calcitonin [7]. When rats were pretreated with EHDP, it also inhibited or abolished the ability of the hormone to reduce the leadinduced plasma calcium and phosphate changes [1]. The suggestion was made in this report that the calcitonin-induced calcium-phosphate compounds found in bone fluid [8] might have a high affinity for…”

“…We have recently reported [1] that if calcitonin were injected 30 min prior to lead acetate injection, both the hypercalcemia and hyperphosphatemia were reduced by as much as 50%. The amount of lead circulating in plasma was similarly reduced.…”