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.

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.

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.

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.

Interaction between parathyroid hormone and prostaglandin E1 on cyclic AMP metabolism in rat kidney

1980 ◽  
Vol 93 (3) ◽  
pp. 339-345 ◽  
Author(s):  
Naokazu Nagata ◽  
Yuriko Ono ◽  
Narimichi Kimura
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Rat Kidney ◽  
Prostaglandin E ◽  
Cortical Tissue ◽  
Newborn Rat ◽  
Simultaneous Addition ◽  
Renal Cortical Tissue ◽  
Subsequent Addition

Abstract. The interaction between parathyroid hormone (PTH) and prostaglandin E1 (PGE1) in influencing cyclic AMP metabolism in rat renal cortical tissue was examined. PTH and PGE1 stimulated additively the adenylate cyclase activity in the homogenate of the tissue. Both PTH and PGE1 enhanced the level of cyclic AMP in the incubated renal cortical tissue, but the effect of their simultaneous addition did not exceed the effect induced by PTH alone. Cyclic AMP accumulated in the incubation medium by stimulation by PTH was decreased by the simultaneous addition of PGE1. When the tissue was pre-incubated for 30 min with 2 to 10 μg/ml of PGE1, the magnitude of the increase of cyclic AMP caused by PTH subsequently added was lessened. However, the response to PTH of adenylate cyclase preparation obtained from the homogenate of PGE1-pre-treated tissue was not decreased. When first PTH was added to the incubating renal cortical tissue, the subsequent addition of PGE1 accelerated the decrease of cyclic AMP content in the tissue and decreased the amount of cyclic AMP released from the tissue. The interaction of PTH and PGE1 on cyclic AMP metabolism in the renal cortical tissue was in contrast to that seen in newborn rat calvaria where PGE1 and PTH acted additively in enhancing the level of cyclic AMP.

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

Cannabinoid effects on adenylate cyclase and phosphodiesterase activities of mouse brain

1977 ◽  
Vol 55 (4) ◽  
pp. 934-942 ◽  
Author(s):  
Thomas W. Dolby ◽  
Lewis J. Kleinsmith
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Mouse Brain ◽  
Biogenic Amine ◽  
Specific Activity ◽  
Intraperitoneal Administration ◽  
The Brain

The experiments presented in this paper examine the mechanisms underlying the ability of cannabinoids to alter the in vivo levels of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in mouse brain. It was found that changes in cyclic AMP levels are a composite result of direct actions of cannabinoids on adenylate cyclase (EC 4.6.1.1) activity and indirect actions involving the potentiation or inhibition of biogenic amine induced activity of adenylate cyclase. Furthermore, the long-term intraperitoneal administration of 1-(−)-Δ-tetrahydrocannabinol to mice produced a form of phosphodiesterase (EC 3.1.4.17) in the brain whose activity is not stimulated by Ca2+, although its basal specific activity is similar to that of control animals. In vitro, the presence of the cannabinoids caused no significant changes in activity of brain PDE at the concentrations tested. Some correlations are presented which imply that many of the observed behavioral and physiological actions of the cannabinoids in mammalian organisms may be mediated via cyclic AMP mechanisms.

MEMBRANES FROM A TRANSPLANTABLE OSTEOGENIC SARCOMA RESPONSIVE TO PARATHYROID HORMONE AND PROSTAGLANDINS: REGULATION OF ADENYLATE CYCLASE AND OF HORMONE METABOLISM

1978 ◽  
Vol 77 (2) ◽  
pp. 213-224 ◽  
Author(s):  
A. CRAWFORD ◽  
N. H. HUNT ◽  
J. K. DAWBORN ◽  
V. P. MICHELANGELI ◽  
T. J. MARTIN
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Osteogenic Sarcoma ◽  
Enzyme Activation ◽  
Steady Increase ◽  
Synthetic Analogue ◽  
Dependent Manner ◽  
High Concentration ◽  
Prostaglandin F

SUMMARY Adenylate cyclase activity in particulate fractions from a transplantable rat osteogenic sarcoma was stimulated in a dose-dependent manner by prostaglandins E1 and E2 (PGE1 and PGE2) and parathyroid hormone (PTH). Prostaglandin F2α was active at a high concentration (3 × 10− 4 mol/l). Pretreatment of membranes with collagenase plus hyaluronidase reduced the magnitude of the PTH effect but did not affect the size of the PGE1 effect. Guanosine 5′-triphosphate and its synthetic analogue 5′-guanylylimidodiphosphate (Gpp(NH)p) activated adenylate cyclase in particulate preparations from the osteogenic sarcoma. The latter agent produced much larger effects, although the concentrations required for half-maximal enzyme activation were the same for both agonists (approximately 2 × 10−6 mol/l). The effects of PTH and Gpp(NH)p were supra-additive at some concentrations of hormone. The effects of PGE1 and Gpp(NH)p were supra-additive at all hormone concentrations tested. Pre-incubation of membrane particles for 6 min with PTH produced an enzyme activation which was not reversed by dilution through washing; pre-incubation with PGE1 did not produce this effect. The response of membrane adenylate cyclase to Gpp(NH)p (10−4 mol/l) was 75% greater in preparations pre-incubated with PTH than in membranes pre-incubated in buffer alone or in buffer containing PGE1. The basal rate of cyclic AMP production in the adenylate cyclase assay system decreased over a 35 min incubation period. This decrease was prevented by addition of PTH or PGE1. Addition of NaF or Gpp(NH)p produced a steady increase in the rate of production of cyclic AMP with time. Membrane preparations did not reduce the biological activity of PTH and did not degrade 125I-labelled PTH. The results demonstrate that the PTH- and PGE-responsive adenylate cyclases of the osteogenic sarcoma have distinctly different properties and that particulate preparations of the tumour do not metabolize PTH.

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