Hyper- and hypocalcemic effects of amino acids in parathyroidectomized rats.

Abstract

Upon subcutaneous injection immediately after parathyroidectomy, valine and tryptophan elevated plasma calcium concentrations and methionine decreased plasma calcium in rats fed on a diet containing 1.76% calcium. The hypercalcemic action of valine and tryptophan became evident 4 hr after injection. In rats with intact parathyroid glands, the hypercalcemic action of valine and tryptophan and the hypocalcemic action of methionine were not demonstrable, suggesting the importance of the parathyroids in calcium homeostasis. Thirteen other amino acids failed to show a measurable effect on plasma calcium in parathyroidectomized rats. {Endocrinology 78:1082,1966) A LTHOUGH the effects of orally adminis-t\. tered amino acids on intestinal absorption of calcium have been pointed out (1), parenteral administration of amino acids has scarcely been used in the study of calcium metabolism, especially with reference to plasma calcium levels. In the course of screening various amino acids for their effect on plasma calcium in rats, definite hypercalcemic effects of valine and tryptophan and a hypocalcemic effect of methionine were observed in parathyroidectomized rats fed on a diet containing 1.76% calcium. Materials and Methods Male Wistar rats of 150-200 g maintained on Oriental Rat Chow containing 1.76% calcium and 200 IU of vitamin D were parathyroidectomized by cautery. Seventeen amino acids: glycine, alanine, valine, leucine, isoleucine, aspartic acid, glutamic acid, arginine, histidine, lysine, threonine, methionine, phenylalanine, tryptophan, tyrosine, proline and hydroxyproline, were dissolved in distilled water, 100 mg/3 ml, with addition of 0.3 ml of 6N NaOH in case of glutamic acid, tyrosine and tryptophan, and subcutaneously injected immediately after parathyroidectomy at a dose of 100 mg/100 g body weight, while similarly parathyroidectomized controls received only distilled water by injection. All animals were sacrificed 6 hr later, and blood samples obtained from the jugular vein were placed in heparinized test tubes. Plasma was separated immediately, and the plasma calcium concentration was determined by stepwise titration with EDTA using a photoelectric colorimeter (2). Valine, tryptophan and methionine were also injected subcutaneously in intact rats, using similarly prepared samples, to determine the effects on plasma calcium 6 hr later. Blood samples were also obtained 1, 2 and 4 hr after injection of valine, Received September 29, 1965. tryptophan and methionine in parathyroidectomized animals. Fifty, 25 and 10 mg of valine, and 50 mg of tryptophan and methionine, were also tested to determine their effect on plasma calcium in parathyroidectomized rats fed on the diet containing 1.76% calcium.