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.

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.

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.

ENDOCRINE EFFECTS OF LITHIUM:

1978 ◽  
Vol 88 (3) ◽  
pp. 528-534 ◽  
Author(s):  
C. Christiansen ◽  
P. C. Baastrup ◽  
P. Lindgreen ◽  
I. Transbøl
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Serum Calcium ◽  
Lithium Treatment ◽  
Serum Magnesium ◽  
Endocrine Effects ◽  
Manic Depressive ◽  
Depressive Patients ◽  
Immunoreactive Parathyroid Hormone

ABSTRACT Ninety-six manic-depressive patients were studied during long-term lithium treatment. Highly significant elevations were observed respecting the levels of serum immunoreactive parathyroid hormone (P < 0.001) as well as the protein-corrected levels of serum calcium (P < 0.001) and serum magnesium (P <0.001), thus indicating a state of 'primary' hyperparathyroidism. The patients as a group had normophosphataemia and normophosphatasia supporting the impression of a rather mild state of biochemical hyperparathyroidism.

Cyclic Amp Response to Parathyroid Hormone during Lithium Treatment

1982 ◽  
Vol 62 (2) ◽  
pp. 34P-34P
Author(s):  
D.G. Waller ◽  
J.D.M. Albano ◽  
J.G.B. Millar ◽  
A. Polak
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Lithium Treatment

Dissociation between plasma, urine, and renal papillary cyclic AMP content following vasopressin and DDAVP

1979 ◽  
Vol 237 (3) ◽  
pp. F218-F225 ◽  
Author(s):  
M. J. Bia ◽  
S. Dewitt ◽  
J. N. Forrest
Keyword(s):  
Cyclic Amp ◽  
Urine Osmolality ◽  
Brattleboro Rats ◽  
Renal Papilla ◽  
Brattleboro Rat ◽  
Clearance Studies ◽  
Urinary Cyclic Amp ◽  
Stimulation Of

The effects of in vivo physiologic doses of vasopressin and 1-deamino-8-D-arginine vasopressin (DDAVP) on the cyclic AMP content of plasma, urine, and renal papillary tissue were determined in the ADH-deficient Brattleboro rat. During clearance studies, plasma cyclic AMP concentrations and both total and nephrogenous urinary cyclic AMP excretion in vasopressin- and DDAVP-treated rats were similar to the values in time-matched controls. In contrast, in situ renal papillary cyclic AMP content was higher (P less than 0.001) in both vasopressin- (35.7 +/- 3.6 pmol/mg protein) and DDAVP- (29.7 +/- 2.2 pmol/mg protein) treated rats compared to controls (15.1 +/- 1.3 pmol/mg protein). Endogenous stimulation of vasopressin by dehydration in normal rats increased both papillary cyclic AMP content (27.1 +/- 2.7 pmol/mg protein) and urine osmolality, whereas no change in papillary cyclic AMP was observed following dehydration in Brattleboro rats (13.6 +/- 0.8 pmol/mg protein) despite an increase in urine osmolality. The results demonstrate that changes in cyclic AMP following in vivo vasopressin are best demonstrated by measurement of in situ cyclic AMP content of the renal papilla, whereas total urinary cyclic AMP and nephrogenous cyclic AMP are not useful indices of tubular sensitivity to this hormone.

Urine osmolality, cyclic AMP and aquaporin-2 in urine of patients under lithium treatment in response to water loading followed by vasopressin administration

2007 ◽  
Vol 566 (1-3) ◽  
pp. 50-57 ◽  
Author(s):  
Ingeborg Wilting ◽  
Ruben Baumgarten ◽  
Kris L.L. Movig ◽  
Jan van Laarhoven ◽  
Alfred J. Apperloo ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Lithium Treatment ◽  
Urine Osmolality ◽  
Water Loading ◽  
Aquaporin 2 ◽  
Response To Water

scholarly journals Lithium-induced NDI: acetazolamide reduces polyuria but does not improve urine concentrating ability

2017 ◽  
Vol 313 (3) ◽  
pp. F669-F676 ◽  
Author(s):  
Theun de Groot ◽  
Joan Doornebal ◽  
Birgitte M. Christensen ◽  
Simone Cockx ◽  
Anne P. Sinke ◽  
...  
Keyword(s):  
Urine Output ◽  
Nephrogenic Diabetes Insipidus ◽  
Filtration Rate ◽  
Collecting Duct ◽  
Urine Osmolality ◽  
Systemic Blood Pressure ◽  
Systemic Blood ◽  
Urine Concentrating Ability ◽  
Concentrating Defect

Lithium is the mainstay treatment for patients with bipolar disorder, but it generally causes nephrogenic diabetes insipidus (NDI), a disorder in which the renal urine concentrating ability has become vasopressin insensitive. Li-NDI is caused by lithium uptake by collecting duct principal cells and downregulation of aquaporin-2 (AQP2) water channels, which are essential for water uptake from tubular urine. Recently, we found that the prophylactic administration of acetazolamide to mice effectively attenuated Li-NDI. To evaluate whether acetazolamide might benefit lithium-treated patients, we administered acetazolamide to mice with established Li-NDI and six patients with a lithium-induced urinary concentrating defect. In mice, acetazolamide partially reversed lithium-induced polyuria and increased urine osmolality, which, however, did not coincide with increased AQP2 abundances. In patients, acetazolamide led to the withdrawal of two patients from the study due to side effects. In the four remaining patients acetazolamide did not lead to clinically relevant changes in maximal urine osmolality. Urine output was also not affected, although none of these patients demonstrated overt lithium-induced polyuria. In three out of four patients, acetazolamide treatment increased serum creatinine levels, indicating a decreased glomerular filtration rate (GFR). Strikingly, these three patients also showed a decrease in systemic blood pressure. All together, our data reveal that acetazolamide does not improve the urinary concentrating defect caused by lithium, but it lowers the GFR, likely explaining the reduced urine output in our mice and in a recently reported patient with lithium-induced polyuria. The reduced GFR in patients prone to chronic kidney disease development, however, warrants against application of acetazolamide in Li-NDI patients without long-term (pre)clinical studies.

Impaired renal response to parathyroid hormone in potassium depletion

1975 ◽  
Vol 228 (1) ◽  
pp. 179-183 ◽  
Author(s):  
N Beck ◽  
BB Davis
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Renal Cortex ◽  
Rat Kidney ◽  
Potassium Depletion ◽  
Dibutyryl Cyclic Amp ◽  
Renal Response ◽  
Proximal Tubular ◽  
Urinary Cyclic Amp

In potassium depletion, a possible alteration of the proximal tubular response to parathyroid hormone (PTH) was evaluated in rat kidney. 1) There were impairments of both phosphaturic and urinary cyclic AMP responses to PTH. The site of the impairment was further investigated by studying the PTH-dependent cycle AMP system in renal cortex. 2) There was a lesser increase of cyclic AMP concentration by PTH in potassium-depleted slices, indicating the lesser urinary cyclic AMP was due to the specific impairment of PTH-dependent cyclic AMP in the kidney. 3). The activation of adenylate cyclase by PTH was impaired , but phosphodiesterase activity was not affected by potassium depletion, indicating the impairment of cyclic AMP generation was due to inhibition of adenylate cyclase. 4) The phosphaturic response to dibutyryl cyclic AMP infusion was also significantly less in the potassium-depleted animals, indicating the step subsquent to the cyclic AMP generation is also impaired. All above results indicate that, in potassium depletion, the renal response to PTH is impaired, and the impairment is both within the step of cyclic AMP generation and after the cyclic AMP generation.

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