Effect of parathyroid hormone on rat heart cells.

A B S T R A C T Cumulative evidence indicates thatthere is an increased accumulation of calcium in dystrophic muscle and that this may have a pathophysiological role in the progression of the dystrophic process. The accumulation may be related to a defect of the plasma membrane. Because parathyroid hormone (PTH) stimulates calcium influx into the cytosol, the chronic effects of surgical ablation of the parathyroid glands on muscle Ca, Mg, protein synthesis, and histology, as well as plasma creatine phosphokinase (CPK), Ca, and Mg, were studied in normal and dystrophic (BIO 14.6) To determine the degree of dystrophy at the age when TPTX was performed, identical analyses were made in 35-d-old hamsters. Definitive histological signs of dystrophy were observed, and although the Ca content in heart, diaphragm, and rectus femoris was elevated, the values were lower than in 90-d-old intact and TPTX dystrophic hamsters. This indicates that chronic TPTX in dystrophic hamsters reduces, but does not arrest, the dystrophic process.In normal hamsters, a 50% reduction in plasma Ca concentration was observed 6 h after TPTX; 55 d after TPTX, however, plasma Ca was within normal limits in both normal and dystrophic hamsters. No parathyroid tissue was observed in serial sections of the trachea and adjacent tissues in TPTX animals. This suggests that in chronically TPTX hamsters fed a standard laboratory diet, plasma Ca can be maintained by mechanisms independent of parathyroid function.The data indicate that in dystrophic hamsters TPTX causes a marked reduction in: (a) muscle Ca accumulation, (b) levels of plasma CPK and, (c) intensity of histological changes in the heart. These changes were independent of the levels of plasma Ca and were not observed in normal hamsters. We conclude that PTH accentuates the dystrophic process, probably by enhancing the already increased Ca flux into muscle (apparently caused by defective sarcolemma). We postulate that normal secretion of PTH may have a deleterious effect in congenital or acquired conditions associated with altered plasma membranes.

Section: Effects Of Acute Tptxsupporting

confidence: 81%

Parathyroid Ablation in Dystrophic Hamsters

Palmieri¹,

Nutting²,

Bhattacharya³

et al. 1981

“…bPTH in a concentration up to 220 U/ml did not inhibit human BFU-E (Table I) and this fragment of PTH also had no effect on mouse marrow progenitor cells, Table II. The same batch of bPTH stimulated the beating ofheart cells (31) and increased the production ofcyclic AMP by renal tubular cells (32) indicating that it was biologically active in other systems.…”

Section: Resultsmentioning

confidence: 98%

Effect of parathyroid hormone on erythropoiesis.

Meytes¹,

Bogin²,

Ma³

et al. 1981

Self Cite

224

112

A B S T R A C T Inhibitors of erythropoiesis have been found in the blood of uremic patients but their nature has not been identified. These patients have excess blood levels of parathyroid hormone (PTH) and it is possible that PTH inhibits erythropoiesis. The present study was undertaken to examine the effect of intact PTH molecules and some of its fragments on human peripheral blood and mouse bone marrow burst-forming units-erythroid (BFU-E), on mouse bone marrow erythroid colony-forming unit (CFU-E), and granulocyte macrophage progenitors (CFU-GM), and evaluate the interaction between PTH and erythropoietin (Ep) on human BFU-E. Intact PTH (1-84 bPTH) in concentrations (7.5-30 U/ml) comparable to those found in blood of uremic patients produced marked and significant (P < 0.01) inhibition of BFU-E and mouse marrow GFU-GM, but not of mouse marrow CFU-E. Inactivation of 1-84 bPTH abolished its action on erythropoiesis. Increasing the concentration of Ep in the media from 0.67 to 1.9 U/ml overcame the inhibitory effect of 1-84 bPTH on BFU-E. The N-terminal fragment of PTH (1-34 bPTH) and 53-84 hPTH had no effect on BFU-E.The results deomonstrate that (a) either the intact PTH molecule or a C-terminal fragment(s) bigger than 53-84 moiety exerts the inhibitory effect on erythropoiesis, and (b) adequate amounts of Ep can overcome this action of PTH. The data provide one possible pathway for the participation of excess PTH in the genesis of the anemia of uremia.

“…Parathyroid hormone is known to augment calcium entry into many cells (25)(26)(27)(28)(29). However, cells are endowed with mechanisms that allow them to pump out the excess calcium and/or buffer it by intracellular organelles (30).…”

Section: Discussionmentioning

confidence: 99%

On the mechanism of impaired insulin secretion in chronic renal failure.

Fadda

Hajjar²,

Perna³

et al. 1991

Self Cite

It has been suggested that a sustained rise in resting levels of cytosolic calcium jCa2+Ji of pancreatic islets is responsible for impaired insulin secretion in chronic renal failure (CRF). Evidence for such an event is lacking and the mechanisms through which it may affect insulin secretion are not known. Studies were conducted in normal, CRF, and normocalcemic, parathyroidectomized (PTX) CRF rats to answer these questions.Resting levels of [Ca2+J1 of islets from CRF rats were higher (P < 0.01) than in control or CRF-PTX rats. [3HJ2-deoxyglucose uptake and cAMP production by islets were not different in the three groups. Insulin content of, and glucose-induced insulin secretion by islets from CRF rats was lower (P < 0.01) than in control and CRF-PTX rats. In contrast, glyceraldehydeinduced insulin release by CRF islets was normal. Basal ATP content, both glucose-stimulated ATP content and ATP/ADP ratio, net lactic acid output, V,, of phosphofructokinase-1, and Ca2"ATPase of islets from CRF rats were lower (P < 0.02-<0.01) than in normal or CRF-PTX animals.Data show that: (a) Glucose but not glyceraldehyde-induced insulin secretion is impaired in CRF; (b) the impairment in glucose-induced insulin release in CRF is due to a defect in the metabolism of glucose; (c) this latter defect is due to reduced ATP content induced partly by high ICa2+J of islets; and (d) the high [Ca2J1i in islets of CRF rats is due to augmented PTH-induced calcium entry into cells and decreased calcium extrusion from the islets secondary to reduced activity of the Ca2" ATPase. (J. Clin. Invest. 1991. 87:255-261.)