Thyrocalcitonin.

The adenylate cyclase [ATP pyrophosphatelyase (cyclizing), EC 4.6.1.1] sensitivity to salmon calcitonin in 11 different segments of the rabbit nephron was investigated using a micromethod for enzyme activity measurements in samples, each containing a single piece of tubule. The required segments were isolated by microdissection from collagenasetreated rabbit kidneys. The results were expressed as femtomoles of adenosine 3':5'-cyclic monophosphate formed per mm of tubular length per 30 min of incubation time. In the presence of 0.1 gg/ml of synthetic salmon calcitonin, it was found that eight segments exhibited no hormonal sensitivity whereas maximal responses were induced in three segments, the "bright" portion of the distal convoluted tubule, the cortical and the medullary portions of the thick ascending limb of the loop of Henle (stimulated over control activity ratios were 32, 11, and 27). The very high sensitivity to calcitonin of the adenylate cyclase contained in these three segments (0.01 ng/ml of salmon calcitonin inducing a 2-fold stimulation; half-maximal stimulation corresponding to about 0.3 ng/ml of salmon calcitonin) suggests that the distal convoluted tubule, as well as the cortical and medullary portions of the thick ascending limb of the loop of Henle represent physiological target structures of calcitonin action within the kidney.It has been shown several times that calcitonin is able to stimulate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6

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“…It (22)(23)(24), the magnitude of which depends on experimental conditions, animal species and the origin of the hormonal preparation used.…”

Section: Discussionmentioning

confidence: 99%

Distribution of calcitonin-sensitive adenylate cyclase activity along the rabbit kidney tubule.

Chabardès¹,

Imbert–Teboul²,

Montegut³

et al. 1976

Proc. Natl. Acad. Sci. U.S.A.

100

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“…Important clinical consequences include bone pain and deformity, pathologic fractures, neurologic deficits, and congestive heart failure. Calcitonin, the polypeptide hormone of ultimobranchial and thyroid parafollicular cell origin, is a powerful in vivo and in vitro inhibitor of bone resorption (2). The present metabolic and clinical study was undertaken to ascertain whether calcitonin is capable of inhibiting the pathologic bone resorption of generalized Paget's disease.…”

Section: Introductionmentioning

confidence: 99%

The clinical and metabolic effects of porcine calcitonin on Paget's disease of bone

Shai¹,

Baker²,

Wallach³

1971

J. Clin. Invest.

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A B S T R A C T The clinical and metabolic effects of porcine calcitonin were assessed in six patients with Paget's disease and two patients with osteoporosis under metabolic balance conditions. The administration of calcitonin for 4-17 wk resulted in an amelioration of the clinical phenomena associated with Paget's disease, including bone pain, increased skeletal vascularity, congestive heart failure, and neurologic deficits secondary to skeletal impingement. The major metabolic effects of calcitonin in Paget's disease included the induction of positive calcium balance of +50 to +240 mg/day, reduction in hyperphosphatasia and hydroxyprolinuria of 15 to 60%, and a deceleration of radiocalcium turnover by 12 to 46%. Natriuresis, phosphaturia, and reduced urinary calcium excretion were observed, whereas sustained hypocalcemia and hypophosphatemia did not occur. The administration of porcine calcitonin was not associated with adverse objective or subjective reactions, toxic effects, or allergic phenomena. There was no evidence of antibody formation or loss of therapeutic potency. Although the response of individual patients with Paget's disease varied widely, the data indicate that calcitonin, presumably through its skeletal anti-resorptive action, is able to reduce skeletal turnover and volume in Paget's disease, and thereby improve the associated clinical and metabolic 'abnormalities. Long term therapeutic studies in progress suggest that prolonged periods of control of the generalized condition may be feasible.

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“…C;tlcitonirl is a polypcptitle Iiorrnoric secreted in m;trnmals hy tlic parafollicul;tr cells of the thyroicl gl~tnrl (30). The major action of calcitonin is to inhihit I>onc resorption (47).…”

Section: Discussionmentioning

confidence: 99%