Protamine-Induced Hypocalcemia

Abstract

Protamine, administered intravenouslyin doses of 5–10 mg/kg, induced hypocalcemia and hypophosphatemia in intact and nephrectomized rats, and hypocalcemia in thyroparathyroidectomized rats. Protamine inhibited parathyroid hormone-induced bone resorption in cultured calvariae of newborn mice, and both acute and long-term studies using 46Ca in the intact rat suggested that protamine also inhibited bone resorption in vivo. Whereas protamine appeared to mimic the action of thyrocalcitonin in the above respects, the mechanism of protamine-induced hypocalcemia probably differs from that of thyrocalcitonin. The dose-response curves for hypocalcemia induced by protamine and by thyrocalcitonin were not parallel. The hypercalcemic effect of dibutyryl cyclic AMP was blocked by protamine, and protamine produced hypocalcemia in the presence of theophylline, suggesting that 3′,5′-cyclic AMP may not be involved. Protamine was apparently cleared from blood, or bound to some fraction of blood, very rapidly; heparin administered 5 min before protamine prevented hypocalcemia, but was ineffective when given 5 min after protamine. The experimental evidence suggests that protamine produces hypocalcemia and hypophosphatemia by direct inhibition of bone resorption. (Endocrinology87:1211, 1970)