Direct Inhibitory Effect of Hypercalcemia on Renal Actions of Parathyroid Hormone

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1974 Mar 1

PMID 4359938

Citations 12

Authors

N Beck

H Singh

S W Reed

B B Davis

Affiliations

Soon will be listed here.

Abstract

The effects of calcium on the renal actions of parathyroid hormone (PTH) were studied in vivo and in vitro. In parathyroidectomized rats, variable levels of blood calcium concentration were induced by intravenous infusion of calcium. The renal responses to the injected PTH, i.e. phosphate and cyclic AMP excretion, were compared in these animals. After PTH injection, the increases of both phosphate and cyclic AMP excretion were less in the calcium-infused animals than in the control group without calcium infusion. There was an inverse correlation between the renal responses to PTH and plasma calcium concentration of 4.2-13.5 mg/100 ml. But calcium had no effect on phosphate excretion induced by infusion of dibutyryl cyclic AMP. In the in vitro experiments, the increase of cyclic AMP concentration in response to PTH was less in renal cortical slices taken from the calcium-infused animals than in ones from the control group without calcium infusion. Calcium also inhibited the activation of renal cortical adenylate cyclase in response to PTH, but calcium had no effect on phosphodiesterase. The data indicate that calcium directly inhibits renal actions of PTH both in vivo and in vitro. Such inhibitory mechanism is probably at or before the step of PTH-dependent cyclic AMP generation in the kidney.

Citing Articles

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Renal refractoriness to PTH in experimental Fanconi syndrome: evidence for intact adenylate cyclase activation.

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Pathogenic role of cyclic AMP in the impairment of urinary concentrating ability in acute hypercalcemia.

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References

CHASE L, Aurbach G . Renal adenyl cyclase: anatomically separate sites for parathyroid hormone and vasopressin. Science. 1968; 159(3814):545-7. DOI: 10.1126/science.159.3814.545. View

CHASE L, Aurbach G . Parathyroid function and the renal excretion of 3'5'-adenylic acid. Proc Natl Acad Sci U S A. 1967; 58(2):518-25. PMC: 335666. DOI: 10.1073/pnas.58.2.518. View

Cheung W . Properties of cyclic 3',5'-nucleotide phosphodiesterase from rat brain. Biochemistry. 1967; 6(4):1079-87. DOI: 10.1021/bi00856a017. View

Agus Z, Puschett J, SENESKY D, Goldberg M . Mode of action of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on renal tubular phosphate reabsorption in the dog. J Clin Invest. 1971; 50(3):617-26. PMC: 291970. DOI: 10.1172/JCI106532. View

Kaneko T, Field J . A method for determination of 3',5'-cyclic adenosine monophosphate based on adenosine triphosphate formation. J Lab Clin Med. 1969; 74(4):682-90. View

Streeto J . Renal cortical adenyl cyclase: effect of parathyroid hormone and calcium. Metabolism. 1969; 18(11):968-73. DOI: 10.1016/0026-0495(69)90037-7. View

Sherwood L, MAYER G, Ramberg Jr C, Kronfeld D, Aurbach G, Potts Jr J . Regulation of parathyroid hormone secretion: proportional control by calcium, lack of effect of phosphate. Endocrinology. 1968; 83(5):1043-51. DOI: 10.1210/endo-83-5-1043. View

Bar H, HECHTER O . Adenyl cyclase and hormone action. 3. Calcium requirement for ACTH stimulation of adenyl cyclase. Biochem Biophys Res Commun. 1969; 35(5):681-6. DOI: 10.1016/0006-291x(69)90459-8. View

SHANNON J, Smith H . THE EXCRETION OF INULIN, XYLOSE AND UREA BY NORMAL AND PHLORIZINIZED MAN. J Clin Invest. 1935; 14(4):393-401. PMC: 424694. DOI: 10.1172/JCI100690. View

10.

Andreucci V, Herrera-Acosta J, RECTOR Jr F, SELDIN D . Measurement of single-nephron glomerular filtration rate by micropuncture: analysis of error. Am J Physiol. 1971; 221(6):1551-9. DOI: 10.1152/ajplegacy.1971.221.6.1551. View

11.

Butcher R . Role of cyclic AMP in hormone actions. N Engl J Med. 1968; 279(25):1378-84. DOI: 10.1056/NEJM196812192792507. View

12.

Nagata N, Rasmussen H . Parathyroid hormone, 3'5' AMP, Ca++, and renal gluconeogenesis. Proc Natl Acad Sci U S A. 1970; 65(2):368-74. PMC: 282912. DOI: 10.1073/pnas.65.2.368. View

13.

Aurbach G, Houston B . Determination of 3',5'-adenosine monophosphate with a method based on a radioactive phosphate exchange reaction. J Biol Chem. 1968; 243(22):5935-40. View

14.

Moore E . Ionized calcium in normal serum, ultrafiltrates, and whole blood determined by ion-exchange electrodes. J Clin Invest. 1970; 49(2):318-34. PMC: 322474. DOI: 10.1172/JCI106241. View

15.

Krishna G, Weiss B, Brodie B . A simple, sensitive method for the assay of adenyl cyclase. J Pharmacol Exp Ther. 1968; 163(2):379-85. View

16.

Yamashita K, Bloom G, Field J . Effects of ions on thyrotrophin and prostaglandin E stimulation of glucose oxidation and adenyl cyclase-cyclic AMP system in dog thyroid slices. Metabolism. 1971; 20(10):943-53. DOI: 10.1016/0026-0495(71)90015-1. View

17.

Nagata N, Rasmussen H . Parathyroid hormone and renal cell metabolism. Biochemistry. 1968; 7(10):3728-33. DOI: 10.1021/bi00850a053. View

18.

CHASE L, FEDAK S, Aurbach G . Activation of skeletal adenyl cyclase by parathyroid hormone in vitro. Endocrinology. 1969; 84(4):761-8. DOI: 10.1210/endo-84-4-761. View

19.

Beck N, Derubertis F, Michelis M, Fusco R, Field J, Davis B . Effect of prostaglandin E 1 on certain renal actions of parathyroid hormone. J Clin Invest. 1972; 51(9):2352-8. PMC: 292402. DOI: 10.1172/JCI107047. View

20.

Beck N, Reed S, MURDAUGH H, Davis B . Effects of catecholamines and their interaction with other hormones on cyclic 3',5'-adenosine monophosphate of the kidney. J Clin Invest. 1972; 51(4):939-44. PMC: 302207. DOI: 10.1172/JCI106888. View