The Effects of Exogenous Parathyroid Hormone on Plasma and Urinary Adenosine 3′,5′-Cyclic Monophosphate in Man

1974 ◽  
Vol 47 (5) ◽  
pp. 481-492 ◽  
Author(s):  
S. Tomlinson ◽  
P. M. Barling ◽  
J. D. M. Albano ◽  
B. L. Brown ◽  
J. L. H. O'Riordan
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Bolus Injection ◽  
Normal Subjects ◽  
Peripheral Vein ◽  
Terminal Part ◽  
Cyclic Monophosphate ◽  
Peripheral Plasma ◽  
Bovine Parathyroid Hormone ◽  
Subsequent Disappearance

1. Administration of highly purified bovine parathyroid hormone (BPTH) (200 MRC units) increased the concentration of adenosine 3′,5′-cyclic monophosphate (cyclic AMP) in the peripheral plasma of normal subjects within minutes, whether the hormone was given as a bolus injection or an infusion. 2. The subsequent disappearance of cyclic AMP from the circulation was also rapid (t1/2 = 14 min) and was associated with a prompt decline (t1/2 = 4.6 min) in the concentration of the ammo-terminal part of BPTH, as measured in a region-specific immunoradiometric assay. 3. The concentration of cyclic AMP in plasma from a renal vein was found to increase more rapidly and to reach a greater peak than plasma from a peripheral vein. 4. The administration of BPTH to anephric subjects caused no increase in cyclic AMP. 5. These investigations indicate that parathyroid hormone can act extremely rapidly, with a short half-life, and that the kidney makes a major contribution to the changes in plasma cyclic AMP induced by the hormone. In addition, they form the basis for the development of a simplified Ellsworth—Howard test, using changes in circulating cyclic AMP after BPTH administration as an index of responsiveness to the hormone.

Reversible Resistance to the Renal Action of Parathyroid Hormone in Man

1976 ◽  
Vol 51 (1) ◽  
pp. 59-69 ◽  
Author(s):  
S. Tomlinson ◽  
G. N. Hendy ◽  
D. M. Pemberton ◽  
J. L. H. O'Riordan
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Intravenous Injection ◽  
Normal Subjects ◽  
Standard Test ◽  
Initial Increase ◽  
Partial Recovery ◽  
Amino Terminal ◽  
Receptor Sites ◽  
Bovine Parathyroid Hormone

1. Normal subjects showed a highly reproducible, rapid increase in plasma adenosine 3′:5′-cyclic monophosphate (cyclic AMP) after an intravenous injection of 200 MRC units of highly purified bovine parathyroid hormone. 2. No significant increase in plasma cyclic AMP was observed after administration of bovine parathyroid hormone to patients with severe chronic renal failure. 3. Even when renal function was not impaired, some patients with primary hyperparathyroidism, who had high concentrations of endogenous parathyroid hormone, showed resistance to bovine parathyroid hormone and when this was injected intravenously it caused only a small increase in plasma cyclic AMP. This resistance was reversible since there was marked improvement in the response after parathyroidectomy, when endogenous parathyroid hormone concentration had fallen. 4. It was possible to reproduce this resistance to the hormone by intravenous infusion of bovine parathyroid hormone into normal subjects. When the hormone (1000 MRC units) was infused over 2 h, after an initial increase there was a progressive decline in plasma cyclic AMP concentration and a fall in urinary cyclic AMP excretion. The response to a standard test stimulus (200 MRC units of bovine parathyroid hormone given as a rapid intravenous injection) was examined at intervals after 1000 units of bovine parathyroid hormone had been infused. Initially, the response was severely impaired; at 4 h, partial recovery had occurred and, 24 h after the infusion, recovery of the response was complete. The resistance was therefore reversible. Infusion of the amino-terminal peptide, fragment 1–34, gave the same effect as infusion of intact hormone. Region-specific assays for the hormone were used to show that the concentration of immuno-assayable hormone remained high during the infusions. 5. The mechanism of this reversible resistance to parathyroid hormone remains to be elucidated; it seems unlikely that circulating hormone fragments could account for the prolonged impairment in the responsiveness to the intact hormone. It is possible that alteration in the formation, intracellular degradation or, perhaps, release of cyclic AMP from the cells, is the cause. Changes in the characteristics of the hormone receptor sites might also explain the phenomenon.

Reversible Resistance to the Renal Action of Parathyroid Hormone in Human Vitamin D Deficiency

1982 ◽  
Vol 62 (4) ◽  
pp. 381-387 ◽  
Author(s):  
I. G. Lewin ◽  
S. E. Papapoulos ◽  
G. N. Hendy ◽  
S. Tomlinson ◽  
J. L. H. O'riordan
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Urinary Excretion ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Deficiency ◽  
Normal Subjects ◽  
Cyclic Monophosphate ◽  
Renal Action ◽  
Plasma Adenosine

1. The response to exogenous parathyroid hormone (PTH) was tested in normal subjects and patients with osteomalacia due to vitamin D deficiency; 200 MRC units of bovine PTH were administered intravenously. 2. The rise in plasma adenosine 3′:5′-cyclic monophosphate (cyclic AMP) and the increase in urinary excretion of cyclic AMP were reduced in the patients with vitamin D deficiency. After treatment with vitamin D the responses returned to normal. 3. It is suggested that this reversible resistance is due to the secondary hyperparathyroidism associated with vitamin D deficiency.

A Saturation Assay Method for Adenosine 3′:5′-Cyclic Monophosphate in Plasma and its Use in Studies of the Action of Bovine Parathyroid Hormone

1974 ◽  
Vol 2 (3) ◽  
pp. 453-455 ◽  
Author(s):  
PETER M. BARLING ◽  
JANET D. M. ALBANO ◽  
STEPHEN TOMLINSON ◽  
BARRY L. BROWN ◽  
J. L. H. O'RIORDAN
Keyword(s):  
Parathyroid Hormone ◽  
Assay Method ◽  
Cyclic Monophosphate ◽  
Bovine Parathyroid Hormone

Cyclic AMP Responses to Parathyroid Hormone and Glucagon during Lithium Treatment

1984 ◽  
Vol 66 (5) ◽  
pp. 557-559 ◽  
Author(s):  
D. G. Waller ◽  
J. D. M. Albano ◽  
J. G. B. Millar ◽  
A. Polak
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Intravenous Injection ◽  
Lithium Treatment ◽  
Endocrine Dysfunction ◽  
Urinary Cyclic Amp ◽  
Urine Concentrating Ability ◽  
Bovine Parathyroid Hormone

1. Inhibition of adenylate cyclase has been proposed as a mechanism for hypothyroidism and nephrogenic diabetes insipidus occurring during lithium treatment, but these disorders are rarely found in the same patients. 2. We have measured plasma levels of adenosine 3′:5′-cyclic monophosphate (cyclic AMP) after an intravenous injection of glucagon in eight patients receiving long term lithium treatment and in six control subjects. Urinary cyclic AMP levels after an intravenous injection of bovine parathyroid hormone (PTH) were also measured in the patients. 3. The plasma cyclic AMP response to glucagon in the patient group was significantly lower than that of the controls. No correlation was demonstrated between the plasma cyclic AMP response after glucagon and the urinary cyclic AMP response after PTH. 4. We have previously shown that impairment of the response to PTH correlates with reduced urine concentrating ability during lithium treatment. In contrast, there was no correlation between the responses to PTH and glucagon in individual patients. These results are consistent with the hypothesis that inhibition of adenylate cyclase is an important factor in lithium-induced endocrine dysfunction.

Plasma adenosine 3′, 5′-cyclic monophosphate: Dose-response to injected bovine parathyroid hormone in man

1976 ◽  
Vol 22 (S1) ◽  
pp. 332-335 ◽  
Author(s):  
I. G. Lewin ◽  
G. N. Hendy ◽  
S. E. Papapoulos ◽  
S. Tomlinson ◽  
J. L. H. O'Riordan
Keyword(s):  
Parathyroid Hormone ◽  
Dose Response ◽  
Cyclic Monophosphate ◽  
Plasma Adenosine ◽  
Bovine Parathyroid Hormone

Control of Renal Tubular Phosphate Reabsorption by Parathyroid Hormone in Man

1977 ◽  
Vol 53 (5) ◽  
pp. 431-438
Author(s):  
D. A. Walker ◽  
S. Joyce Davies ◽  
K. Siddle ◽  
J. S. Woodhead
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Primary Hyperparathyroidism ◽  
Normal Subjects ◽  
Vitamin D Metabolism ◽  
Phosphate Reabsorption ◽  
Important Regulator ◽  
Urinary Cyclic Amp ◽  
Renal Tubular

1. The maximum tubular reabsorption capacity for phosphate relative to glomerular filtration rate (Tm,P/GFR) was found to range from 0·8 to 1·5 mmol/l in 32 normal fasting subjects. In 14 patients with primary hyperparathyroidism and five patients with hyperparathyroidism secondary to vitamin D deficiency or malabsorption values ranged from 0·2 to 0·8 mmol/l. 2. Plasma parathyroid hormone concentrations measured by an immunoradiometric technique ranged from <0·15 to 0·9 ng/ml in the normal subjects and from 0·5 to 10 ng/ml in the patients with hyperparathyroidism. There was no correlation, however, between plasma parathyroid hormone and Tm,P/GFR in either normal or abnormal groups. 3. Plasma parathyroid hormone was lower in 11 out of 13 patients with primary hyperparathyroidism 3 or 4 weeks after tumour removal than immediately before the operation. In all cases there was a rise in Tm,P/GFR, though not all values were normalized. 4. Changes in plasma parathyroid hormone, Tm,P/GFR and plasma and urinary cyclic AMP concentrations were measured during infusion of bovine parathyroid hormone into normal fasting subjects. Phosphate reabsorption fell markedly in response to low doses of parathyroid hormone (0·5 i.u. h−1 kg−1), higher doses (4 i.u. h−1 kg−1) producing little additional change in Tm,P/GFR despite large changes in cyclic AMP excretion. At the highest doses used (8 i.u. h−1 kg−1) apparent saturation of the renal adenylate cyclase occurred. During an infusion of hormone, 0·25 i.u. h−1 kg−1 over 3 h, a fall in Tm,P/GFR was recorded at concentrations of immunoreactive parathyroid hormone within the normal range for endogeneous hormone. At such concentrations it was not possible to detect significant changes in either plasma or urine cyclic AMP. 5. It is concluded that parathyroid hormone is an important regulator of renal phosphate handling under normal physiological conditions. Such a regulatory process has been implicated in the control of vitamin D metabolism.

Impairment of Cyclic AMP Response to Bovine Parathyroid Hormone in Patients on Chronic Lithium Therapy with Diminished Renal Urine-Concentrating Ability

1983 ◽  
Vol 64 (6) ◽  
pp. 623-627 ◽  
Author(s):  
D. G. Waller ◽  
J. D. M. Albano ◽  
J. G. B. Millar ◽  
A. Polak
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Intravenous Injection ◽  
Lithium Treatment ◽  
Urine Osmolality ◽  
Control Subjects ◽  
Urinary Cyclic Amp ◽  
Urine Concentrating Ability ◽  
Bovine Parathyroid Hormone

1. Urinary and plasma levels of adenosine 3′:5′-cyclic monophosphate (cyclic AMP) after an intravenous injection of bovine parathyroid hormone (PTH) were measured in 12 patients on long-term lithium treatment and in nine control subjects. The maximum urine osmolality (Umax.) after an intravenous injection of desamino-d-arginine vasopressin (DDAVP) was also measured. 2. in all the control subjects and six of the patients, the Umax. after DDAVP exceeded 700 mosmol/kg. The cyclic AMP responses in these two groups did not differ significantly. 3. in the remaining six patients whose Umax. did not reach 700 mosmol/kg, the cyclic AMP response to PTH was significantly less than that of the controls. 4. A strong correlation was demonstrated in the patients between the urinary cyclic AMP response after PTH and the maximum osmolality after the administration of DDAVP. 5. These observations are consistent with the hypothesis that reduced adenylate cyclase activity contributes to the development of nephrogenic diabetes insipidus in patients on long-term lithium treatment.

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