Direct Inhibitory Effect of Hypercalcemia on Renal Actions of Parathyroid Hormone

Beck, Nama; Singh, Harbans; Reed, Sarah W.; Davis, Bernard B.

doi:10.1172/jci107610

Cited by 68 publications

(30 citation statements)

References 25 publications

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“…In acute PTX rats such a relationship is abolished (16 (7). The experi-mental approach of the possible modulation by calcium concentration of the Ac-cAMP system is made difficult by: (a) the ignorance of the alterations in intracellular calcium concentration in response to changes in the extracellular one, although an increase in extracellular calcium has been postulated to increase intracellular calcium, through enhanced cellular uptake of calcium (28); (b) the reported discrepancies in calcium action on Ac activity in vitro, inhibition by high calcium concentrations being observed in broken cells (11)(12)(13)(14) but not in intact ones (29), (which suggests that the effect of calcium obtained in vitro cannot be extrapolated to the physiological mechanisms in vivo); (c) the administration of exogenous cAMP, which does not necessarily induce events identical to those determined by stimulation of intracellular cAMP synthesis. It is, however, well documented that increasing extracellular cAMP concentration decreases phosphate reabsorption, as does PTH via the Ac-cAMP system (1,(30)(31)(32)(33).…”

Section: Results Of Ultrafiltration Experimentsmentioning

confidence: 99%

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Evidence for a parathyroid hormone-independent calcium modulation of phosphate transport along the nephron.

Amiel¹,

H²,

Couette³

et al. 1976

J. Clin. Invest.

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A B S T R A C T To disclose a parathyroid-independent calcium modulation of phosphate transport along the nephron, the effect of increasing plasma calcium concentration to subnormal levels in rats 6 days after parathyroidectomy (chronic PTX) was studied. Fractional phosphate reabsorption was significantly increased. The whole kidney response to calcium infusion was similar whether or not the thyroid gland was removed, which suggests that calcitonin is not involved. The micropuncture study indicated an increase in the reabsorptive capacity for phosphate (absolute reabsorption/absolute delivered phosphate per nephron segment) in the proximal tubule, the loop, and the terminal nephron when calcium was infused. Thus, the level of plasma calcium or some related factor affects the phosphate transport by the tubule independently of parathyroid hormone.With calcium infusion, the profile of phosphate reabsorption along the nephron became close to that of acutely parathyroidectomized rats, but with persisting differences. The level of plasma calcium concentration may partly account for the differences between the acute and the chronic steps of parathyroidectomy.The role of possible interferences between alterations of extracellular calcium concentration or some related factor and the adenylate cyclase-cyclic AMP system in such an action of calcium was evaluated. Cyclic AMP was infused so as to achieve a 10 M plasma concentration. Combined infusions of calcium and cyclic AMP were also performed. The results are compatible with calcium inhibition of adenylate cyclase, although they do not rule out a direct action of calcium.

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Section: Results Of Ultrafiltration Experimentsmentioning

confidence: 99%

“…Indeed there are several evidences of an influence of calcium on Ac activity (11)(12)(13)(14). Conversely, calcium may act independently of this system, through a pathway insensitive to PTH (7).…”

Section: Introductionmentioning

confidence: 99%

Evidence for a parathyroid hormone-independent calcium modulation of phosphate transport along the nephron.

Amiel¹,

H²,

Couette³

et al. 1976

J. Clin. Invest.

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“…* P < 0.01 as compared to the control value. 5'-AMP, which is a metabolic derivative of cyclic AMP without its biological effect (22), further suggests that the inhibitory effect of cyclic AMP on carbonic anhydrase is related to the biological effect of the nucleotide.…”

Section: Discussionmentioning

confidence: 99%

“…The methods to measure adenylate cyclase activity and phosphodiesterase activity have been described previously in detail (22). Protein concentration was measured by the method of Lowry, Rosebrough, Farr, and Randall (23).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro.

Beck¹,

Kim²,

Wolak³

et al. 1975

J. Clin. Invest.

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A B S T R A C T It has been demonstrated that parathyroid hormone (PTH) inhibits the proximal tubular reabsorption of bicarbonate, and increases the urinary excretion of that ion. There is also a qualitative similarity between the alterations of the proximal tubular reabsorption of phosphate, sodium, and water after PTH administration and after acetazolamide administration. These findings suggest that the renal effect of PTH is possibly mediated through the inhibition of carbonic anhydrase in proximal tubules. Therefore, a possible inhibitory effect of PTH on carbonic anhydrase was evaluated in the homogenate of rat renal cortex by an indicator titration method.Incubation of cortical homogenates with PTH for 10 min at 370C inhibited carbonic anhydrase activity. The inhibitory effect of PTH was ATP-, Mg"+-, and K+-dependent and temperature-dependent; inactivation of PTH by heating at 100'C abolished the effect of PTH both to activate adenylate cyclase and to inhibit carbonic anhydrase. Calcium 5 mM also partially abolished effects of PTH to activate adenylate cyclase and to inhibit carbonic anhydrase. The inhibitory effect of PTH on carbonic anhydrase was specific to renal cortex.Cyclic AMP, the intracellular messenger substance for PTH, also inhibited carbonic anhydrase in renal cortex. The cyclic AMP-induced inhibition was also Mg"+ dependent and temperature dependent, and required preincubation at 370C. But 5'-AMP, a metabolic derivative of cyclic AMP without its biological effect, had no inhibitory effect on carbonic anhydrase.All the above results are consistent with the hypothesis that PTH inhibits proximal tubular reabsorption of bicarbonate and phosphate through the inhibition of

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“…centrations are decreased, PTH secretion and phosphate secretion are reduced. PTH also increases the transport of calcium across the basolateral renal cell membrane and increases intracellular calcium which inhibits the formation of CAMP, thus decreasing the phosphaturic effects of PTH (2,35). PTH is capable of stimulating inositol triphosphate and diacylglycerol production in renal tubular cells (33).…”

Section: Biologic Actions: Kidneymentioning

confidence: 99%

Recent Advances in the Structure and Function of the Parathyroid Gland in Animals and the Effects of Xenobiotics

Capen

Rosol

1989

Toxicol Pathol

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Parathyroid glands in animals consist of a single basic type of secretory cell concerned with the elaboration of one hormone. Parathyroid hormone is the principal hormone involved in the minute-to-minute fine regulation of blood calcium in mammals. A larger biosynthetic precursor of parathyroid hormone is first synthesized on ribosomes of the endoplasmic reticulum in chief cells. Pre-proparathyroid hormone is rapidly converted to proparathyroid hormone in the Golgi apparatus. Active parathyroid hormone is packaged into membrane-limited secretory granules that are stored in the cytoplasm until secretion is stimulated. Parathyroid cells in most animals store relatively small amounts of preformed hormone but are capable of responding to minor fluctuations in calcium ion concentration by rapidly alt'ering the rate of hormonal synthesis and secretion. Recently synthesized and processed active parathyroid hormone may be released directly in response to increased demand and bypass the storage pool of mature secretory granules. Relatively few chemicals or experimental manipulations significantly increase the incidence of parathyroid tumors. Irradiation increases the development of parathyroid adenomas in rats and the incidence is modified by feeding diets with variable amounts of vitamin D. Parathyroid adenomas have been encountered infrequently following the administration of a variety of chemicals in 2-year bioassay studies in Fischer rats; however, the incidence increases dramatically when comparing 2-year studies to lifetime data.

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Direct Inhibitory Effect of Hypercalcemia on Renal Actions of Parathyroid Hormone

Cited by 68 publications

References 25 publications

Evidence for a parathyroid hormone-independent calcium modulation of phosphate transport along the nephron.

Evidence for a parathyroid hormone-independent calcium modulation of phosphate transport along the nephron.

Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro.

Recent Advances in the Structure and Function of the Parathyroid Gland in Animals and the Effects of Xenobiotics

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