Alexander D. Kenny

Effect of crude thyrocalcitonin on calcium and phosphorus metabolism in rats.

Summary Crude thyrocalcitonin when injected subcutaneously into rats caused a hypocalcemia accompanied by a hypophosphatemia and a phosphaturia. There was no increase in urinary calcium indicating that the kidney plays no role in the hypocalcemic response. The calcium content of the kidney fell, an effect which probably reflects the hypocalcemic response and could have clinical importance. The kidney phosphorus content as well as the calcium and phosphorus contents of the small intestine, submaxillary salivary glands, and the lens were not consistently affected by the drug. The data also support the conclusion that calcium transport in the gut plays no role in the hypocalcemic response.

EFFECT OF CATECHOLAMINES ON SERUM CALCIUM AND PHOSPHORUS LEVELS IN INTACT AND PARATHYROIDECTOMIZED RATS.

SummaryThe effects of the catecholamines, epinephrine, norepinephrine and isoproterenol, on serum calcium and phosphorus levels have been studied in intact, and 1-day-parathyroidectomized, fed rats at 1 to 2 hours after subcutaneous injection of the drugs.In intact rats a hypophosphatemic response was seen 1 hour after administration of from 0.01 to 5.0 mg/kg of either isoproterenol or epinephrine, the former being the more potent agent. Norepinephrine had no effect on the serum phosphorus level, even at doses as high as 5.0 mg/kg. None of the three drugs had an effect on the serum calcium levels except that at doses of 1.0 and 5.0 mg/kg epinephrine exhibited a very slight hypercalcemia.In rats which had been parathyroidectomized 24 hours earlier all three agents gave a hypophosphatemic response 2 hours after injection. The high dose, 5.0 mg/kg, of epinephrine and norepinephrine resulted in a hyperphosphatemia. In contrast to the finding in intact animals the parathyroidectomized rats responded to all three catecholamines with a definite hypercalcemia, the order of potency being isoproterenol > epinephrine > norepinephrine.The hypophosphatemic response was antagonized by nethalide, an agent which blocks β receptors. Phenoxybenzamine was ineffective as a blocking agent. Both responses may be classified as β responses within the concept of Ahlquist.

Thyrocalcitonin preparations: Characterization of the depressor contaminant☆

Abstract Previous work from this laboratory has demonstrated that certain preparations of the thyroid hormone, thyrocalcitonin, contain a potent depressor agent. It was also shown that the depressor activity was not associated with the hypocalcemic hormone. The object of this study was to characterize further the nature of the depressor contaminant. It was found that the response of the dog mean arterial blood pressure to intravenous administration of the vasoactive thyrocalcitonin preparations was only partially blocked by the antihistamine, diphenhydramine. The thyrocalcitonin preparations caused a contraction of the guinea pig ileum; this response was effectively blocked by diphenhydramine. It is concluded that histamine or a histamine-like agent is an importan contaminant of certain thyrocalcitonin preparations; the bioassay data indicated a histamine concentration of around 3 μg/ml. However, the fact that diphenhydramine only partially blocked the depressor response does not permit the conclusion that all of the depressor activity is due to a histamine-like agent.

Factors affecting the calcium and phosphorus content of rat lens.

In the course of a study of calcium and phosphorus metabolism in the rat lens, we noticed that the control levels varied within wide limits. In an investigation of possible environmental factors that might influence these control levels, we were unable to implicate changes in either diet or room temperature. Treatment with a long-acting penicillin preparation restored the calcium and phosphorus contents of the lenses to levels of around 2·5 and 80 mg/100 g wet weight, respectively. On the basis of these data, we tentatively conclude that a chronic infection can lead to marked changes in the calcium and phosphorus content of the rat lens.

Effect of adrenalectomy on hyperglycemic responses of fed and fasted rats to catecholamines.

Summary Adrenalectomy in rats has been shown to enhance the hyperglycemic response mediated by the β-receptor (isoproterenol in the fasted rat) but not that mediated by the α-receptor (norepinephrine in the fed rat). The enhanced β-effect is apparently the result of a greater depletion of muscle glycogen. Hyperglycemic responses to epinephrine in fasted animals are enhanced in the lower dose range and depressed at higher doses. This is explained in terms of the effect of epinephrine on both α- and β-receptors. The importance of using both fed and fasted rats and dose-response curves rather than single doses in assessing the effects of adrenalectomy is demonstrated.