Effects of Dibutyryl Cyclic Adenosine 3′,5′-Monophosphate and Parathyroid Extract on Calcium and Phosphorus Metabolism in Hypoparathyroidism and Pseudohypoparathyroidism

Bell, Norman H.; Avery, Susan; Sinha, Tushar; Clark, Charles M.; Allen, Donald O.; Johnston, C. Conrad

doi:10.1172/jci106876

Cited by 84 publications

(22 citation statements)

References 25 publications

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“…Our experiments are at variance with those of Nagata and Rasmussen (9), who found that Fig. 4 Previous studies have shown that the phosphaturic action of PTH in TPTX rats can be produced through infusion of either dibutyryl cyclic AMP (2,(28)(29)(30) or theophylline (28). In addition, it has been reported that the phosphaturic response to both PTH and dibutyryl cyclic AMP is blunted in the D-deficient rat (2).…”

Section: Methodssupporting

confidence: 47%

Renal adenylate cyclase and the interrelationship between parathyroid hormone and vitamin D in the regulation of urinary phosphate and adenosine cyclic 3',5'-monophosphate excretion.

Forte¹,

Nickols²,

Anast³

1976

J. Clin. Invest.

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A B S T R A C T This study examined the role of cyclic AMP in the phosphaturic response to parathyroid hormone in vitamin D-deficient rats. Infusion of purified bovine parathyroid hormone (13.3 Ihg/h) into control, D-fed, or D-deficient, thyroparathyroidectomized rats produced a sixfold increase in renal phosphate and cyclic AMP excretion in D-fed rats, but only a two-to threefold increase in both parameters in D-deficient animals. Intravenous injection of parathyroid hormone over the dosage range from 1-50 Ag/kg resulted in a dosedependent increase in phosphate and cyclic AMP excretion with both D-fed and D-deficient thyroparathyroidectomized rats. However, the D-deficient rats responded to these injections of parathyroid hormone with a two-to threefold increase in both renal phosphate and cyclic AMP excretion at the highest dose of 50 Ag/kg, whereas the D-fed animals' response was 35-fold and 11-fold over control excretion levels of phosphate and cyclic AMP, respectively. To directly examine the role of the renal cortical adenylate cyclase system in the blunted phosphaturic and urinary cyclic AMP responses to parathyroid hormone in D-deficient rats, we prepared a plasma membrane fraction enriched in this enzyme activity from the renal cortex of D-fed and D-deficient thyroparathyroidectomized rats. The renal cortical adenylate cyclase of D-deficient rats showed significantly (P < 0.001) less activation by parathyroid hormone over the hormone concentration range from 0.3 to 7.0 yg/ml than was observed with the enzyme prepared from D-fed animals. Basal adenylate cyclase activity and the fluoride-stimulated enzyme activity were not altered by the state of D-deficiency. These experiments demonstrate that the blunted phosphaturic response to parathyroid hormone observed in D-deficient rats is associated with the reduced responsiveness of the renal cortical adenylate cyclase to the hormone. Moreover, the defect in the renal membrane adenylate cyclase system appears to be localized at the level of PTH binding to membrane receptors or, alternatively, at the level of transmission of the hormone-receptor binding signal to the catalytic moiety of this membrane enzyme.

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Section: Methodssupporting

confidence: 47%

Renal adenylate cyclase and the interrelationship between parathyroid hormone and vitamin D in the regulation of urinary phosphate and adenosine cyclic 3',5'-monophosphate excretion.

Forte¹,

Nickols²,

Anast³

1976

J. Clin. Invest.

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“…The impairment of the adenylate cyclase system in PHP is well known (Chase et al 1969;Bell et al 1972). Drezner et al (1973) classified PHP into 2 types; impairment of an increase in intracellular cAMP (Type I), an inability of intracellular CAMP to initiate the chain of metabolic events (Type II).…”

Section: Discussionmentioning

confidence: 99%

Stimulation of 1,25-dihydroxyvitamin D production by parathyroid hormone and dibutyryl 3',5'-cyclic AMP in normal subjects,hypoparathyroidism and pseudohypoparathyroidism.

Unakami

Furukawa

Sohn

et al. 1982

Tohoku J. Exp. Med.

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“…Several studies have documented the role of cAMP in mediating the phosphaturic response of PTH at the kidney level in man and experimental animals (1 1, 12, 16,25,30). Administration of cAMP has been shown to mimic the phosphaturic effect of PTH in vivo (4,30), and in vitro (3,15). An increase in adenylate cyclase activity and accumulation of intracellular cAMP after PTH administration have been demonstrated (16,26).…”

Section: Resultsmentioning

confidence: 99%

Urinary Excretion of Cyclic Nucleotides and Phosphate in Response to Parathyroid Hormone and Calcitonin in Man

et al. 1981

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SummaryThe response to parathyroid hormone (PTH) and calcitonin (CT) was studied in eight children with various bone diseases by determining the serum calcium (Ca) and phosphate (P) concentration, urinary phosphate excretion rate, renal phosphate clearance, the percentage of filtered phosphate reabsorbed by the renal tubule (%TRP), creatinine clearance (Ccr), urinary cyclic adenosine 3',5' monophosphate excretion rate (UcA~pV), and urinary cyclic guanosine 3',5' monophosphate excretion rate (Ucc~pV). Administration of PTH caused no significant change in serum Ca and P values, whereas CT produced a decrease ih Ca (A Ca, -1.4 + 0.1 mg/100 ml) and P (AP; -1.1 + 0.1 mg/100 ml). There was an increase in U c~~p V ( A U r~~p V ; 437 74 nmoles/min/100 ml Ccr) without any significant change in UcCMpV after administration of PTH. Phosphaturia was produced by both PTH (A TRP, -18 k 3%) and CT (ATRP, -13 -t 2%). However, CT did not elicit any increase in either U c~~p V or U c~~p V . SpeculationParathyroid hormone (PTH) and calcitonin (CT) induce phosphaturia of a similar magnitude whereas PTH alone increased the urinary excretion of cyclic adenosine 3',5' monosphosphate (CAMP). The phosphaturia induced by CT may not be mediated by a similar mechanism involving the adenylate cyclase-CAMP system as demonstrated for PTH.Parathyroid hormone (PTH) and calcitonin (CT) have opposing effects on bone resorption; PTH induces hypercalcemia by stimulating bone resorption whereas CT induces hypocalcemia by inhibiting bone resorption. Despite their opposing effects on bone, they both act on the kidney to produce phosphaturia. The actions of PTH and CT on both bone and kidney are presumably mediated through the adenylate cyclase cyclic adenosine 3',5'-monophosphate (CAMP) system. Studies have shown increased renal formation and urinary excretion of cAMP in response to PTH (1 I, 12). This change in the urinary excretion of cAMP is considered a qualitative indicator of the effect of PTH on the kidney (8,22,32). Some studies also have shown an increase in the formation of cAMP in the kidney after CT administration (20,27). However, few studies have investigated urinary excretion of cAMP after CT administration, and those that are available, report conflicting results. No increase in urinary excretion of cAMP was reported after CT administration in parathyroiaectomized rats, dogs (I I), and in one patient with hypoparathyroidism (28), whereas an increase in cAMP was reported in hamsters (23) and parathyroidectomized rats (24). Some studies in man (1, 2, 28) have shown an increase in urinary cAMP in response to salmon or porcine CT, but the magnitude of rise was insignificant when compared to the rise after PTH. Therefore, to assess the relationship of urinary cAMP excretion and the phosphaturic response to CT in man, we have studied the effect of synthetic human CT on patients with various bone diseases, all of whom had normal phosphaturic and cAMPuric responses to PTH. In view of the possible role of cyclic guanosine 3',Sf-monophosphate (c...

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Effects of Dibutyryl Cyclic Adenosine 3′,5′-Monophosphate and Parathyroid Extract on Calcium and Phosphorus Metabolism in Hypoparathyroidism and Pseudohypoparathyroidism

Cited by 84 publications

References 25 publications

Renal adenylate cyclase and the interrelationship between parathyroid hormone and vitamin D in the regulation of urinary phosphate and adenosine cyclic 3',5'-monophosphate excretion.

Renal adenylate cyclase and the interrelationship between parathyroid hormone and vitamin D in the regulation of urinary phosphate and adenosine cyclic 3',5'-monophosphate excretion.

Stimulation of 1,25-dihydroxyvitamin D production by parathyroid hormone and dibutyryl 3',5'-cyclic AMP in normal subjects,hypoparathyroidism and pseudohypoparathyroidism.

Urinary Excretion of Cyclic Nucleotides and Phosphate in Response to Parathyroid Hormone and Calcitonin in Man

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