The effect of ACTH on calcium distribution in the perfused cat adrenal gland.
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1. Experiments were carried out to study the effects of adrenocorticotrophin (ACTH) on calcium distribution in the isolated cat adrenal gland perfused with Locke solution.2. The addition of ACTH to Locke solution caused a small, but significant, increase in the radiocalcium ((45)Ca) space and content of the adrenal cortex.3. The average (45)Ca washout curve obtained after exposure to ACTH was significantly displaced above the average washout curve for the control glands during the first 20 min of washout. During the time that the two curves were significantly different, maximum corticosteroid secretion was attained.4. The rate of (45)Ca efflux was slowed after ACTH was added to the perfusion medium.5. The total calcium content of the cortex was not altered by ACTH.6. Perfusion with calcium-free Locke caused a rapid decrease in the calcium content of the cortex to about 20% of the control value. Dinitrophenol was required to deplete completely the cortical calcium content during perfusion with the calcium-deprived medium.7. The results are consistent with the suggestion that a translocation of calcium occurs during stimulation of the cortex by ACTH. The source of the calcium ions needed to support the secretory response to ACTH is probably not the extracellular fluid; but ACTH may shift calcium from a rapidly exchanging to a more slowly exchanging cellular pool. (+info)
Effect of cortisone treatment on the active transport of calcium by the small intestine.
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It is generally recognized that glucocorticoid administration may diminish calcium absorption in vivo as well as the active transport of calcium by the intestine in vitro. Recent studies by others have emphasized the possibility of an alteration in the metabolism of vitamin D to 25-hydroxycholecalciferol in accounting for the steroid effects on calcium absorption. The results obtained in the present studies fail to support this hypothesis. The present studies confirm that the administration of cortisone or other glucocorticoids to the rat interferes with the active transport of calcium by duodenal gut sacs in vitro. This abnormality is not due to an alteration in the permeability of the intestine to calcium, and it cannot be corrected by the administration of either massive doses of vitamin D(2) or modest doses of 25-hydroxycholecalciferol. Experiments concerned with the effects of cortisone on the level of the vitamin D-dependent duodenal calcium-binding protein, the amount of bioassayable vitamin D activity in the mucosa, and the distribution and metabolism of (3)H-vitamin D(3), did not provide evidence in favor of a harmone-related defect in either the localization of vitamin D or its metabolism to 25-hydroxycholecalciferol. Alterations in the transport of iron and D-galactose, not dependent on vitamin D, suggest that cortisone treatment may be responsible for more than a simple antagonism to the effects of vitamin D. The results of the present studies indicate that cortisone administration affects the cellular mechanisms mediating calcium transport in a manner that is opposite to the effects of vitamin D, but seems to be independent of any direct interaction with the parent vitamin or its metabolites. If a disorder in vitamin D metabolism is at all involved, it is at a step subsequent to 25-hydroxylation. (+info)
Calcium binding by human erythrocyte membranes.
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1. The characteristics of Ca(2+) binding to haemoglobin-free human erythrocyte membranes were investigated by using (45)Ca and centrifugation partition of ;ghosts' from their external incubation medium. Equilibrium of ;ghosts' with external Ca(2+) required less than 15min. 2. The binding did not vary with temperature in the range 0-37 degrees C. 3. At pH7.4 ;ghosts' bound a maximum of 283mumol of Ca(2+)/g of ;ghost' protein, equivalent to 6.85x10(7) Ca(2+) ions per cell. 4. Increasing the ionic strength from 0.01 to 0.46 diminished Ca(2+) binding, as did ATP in concentrations ranging from 0 to 15mm in the incubation medium. 5. An increase of the pH from 3.0 to 9.3 caused a marked increase in the amount of Ca(2+) bound. 6. Extraction of (45)Ca-labelled ;ghosts' with chloroform-methanol showed that the distribution of Ca(2+) was: 79% protein-bound, 16% lipid-bound, 5% in the aqueous phase, presumably non-bound. Most of the lipid-bound Ca(2+) (about 80%) was associated with a phospholipid fraction containing phosphatidylserine, phosphoinositides and phosphatidylethanolamine, giving a molar Ca(2+): phosphorus ratio of about 1:2. (+info)
Role of calcium and adenosine-3':5'-cyclic monophosphate in controlling fly salivary gland secretion.
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The action of 5-hydroxytryptamine (5-HT) on an insect salivary gland was associated with a rise in adenosine-3':5'-cyclic monophosphate (cAMP) concentration and an increase in calcium uptake. An increase in secretion induced either by 5-HT or exogenous cAMP required extracellular calcium. Both 5-HT and exogenous cAMP increased (45)Ca efflux from previously labeled glands, but only 5-HT caused an increase in calcium uptake. The transepithelial potential in this tissue became more negative after addition of 5-HT, but more positive after addition of cAMP. 5-HT and cAMP induced a more negative potential when calcium was removed from the medium. It was concluded that both calcium and cAMP serve as intracellular messengers when 5-HT acts upon fly salivary gland. (+info)
Short- and long-term effects of estrogen and synthetic anabolic hormone in postmenopausal osteoporosis.
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In 29 women with postmenopausal osteoporosis, the proportion of total bone surface undergoing resorption or formation was evaluated by microradiography of iliac crest biopsy samples before and after short-term (2(1/2)-4 months) and long-term (26-42 months for estrogen and 9-15 months for anabolic hormone) treatment. After estrogen administration, values for bone-resorbing surfaces decreased, although less prominently after long-term than after short-term therapy. The magnitude of this decrease was positively correlated with the pretreatment value for bone-resorbing surfaces (P < 0.001). When the pretreatment value for bone-resorbing surfaces was used as a covariable, estrogen and anabolic hormone appeared to be equally effective. For bone-forming surfaces, short-term therapy with either hormone had no effect but long-term therapy significantly decreased the values. Serum immunoreactive parathyroid hormone (IPTH) increased significantly after estrogen therapy; the change in IPTH was inversely related to the change in serum calcium (P < 0.001, sign test). We conclude that the primary effect of sex hormones in postmenopausal osteoporosis is to decrease the increased level of bone resorption, perhaps by decreasing the responsiveness of bone to endogenous parathyroid hormone. However, this favorable effect, at least in part, is negated after long-term treatment by a secondary decrease in bone formation. Our data are consistent with the concept that the maximal benefit that can be derived from sex hormone therapy in postmenopausal osteoporosis is arrest or slowing of the progession of bone loss. (+info)
The nature of the positive inotropic response of the isolated frog heart to theophylline and to iminazole.
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1. The mechanism of the positive inotropic responses to theophylline and to iminazole has been examined in the frog heart.2. Both theophylline and iminazole caused positive inotropic effects which declined to control amplitude with time despite continued exposure to the drugs. The duration of the response to iminazole was always longer than that to theophylline.3. On washout of theophylline and iminazole the amplitude of heart beat slowly decreased to a value below that in the control period.4. The theophylline response was not prevented by phentolamine or by propranolol given separately or in combination.5. Theophylline potentiated the staircase and prolonged the post-stimulation potentiation phenomena when its own inotropic activity had subsided but iminazole reduced the staircase effect at this time.6. Theophylline, iminazole and 3 x [Ca(2+)](o) all increased the influx of (45)Ca into isolated ventricles. Theophylline increased but iminazole and 3 x [Ca(2+)](o) slightly reduced (45)Ca efflux.7. Total cell calcium changes were only detected in ventricles exposed for 15 min to 3 x [Ca(2+)](o) or theophylline (5 x 10(-3)M). After 60 min exposure to theophylline the total cell calcium was not significantly different from controls.8. It is concluded that the positive inotropic responses to theophylline and iminazole can be interpreted in terms of the increased calcium influx which they produce and that interpretation of effects in terms of their action on phosphodiesterase should be treated with reservation. (+info)
Metabolism of 1,25-dihydroxycholecalciferol in the rat.
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Administration of 60 pmoles of 1,25-dihydroxycholecalciferol to vitamin D-deficient rats on a low calcium diet gives a maximal intestinal calcium transport response in 7 hr and a maximal bone calcium mobilization response in 12 hr. During the 48 hr after injection of radioactive 1,25-dihydroxycholecalciferol, unchanged 1,25-dihydroxycholecalciferol accounts for 71-98% of the radioactivity found in the intestine with minor amounts appearing in more polar metabolites. In the bone, for the 1st 12 hr, 1,25-dihydroxycholecalciferol is the major form (75-82%) present while at 24 hr, the amount of 1,25-dihydroxycholecalciferol decreases with a corresponding rise in the amounts of metabolites both less polar and more polar than the 1,25-dihydroxycholecalciferol. Since these metabolies are at their highest concentration when bone calcium mobilization is decreasing, they are most likely not responsible for the calcium mobilization observed during the 1st 12 hr. The appearance of water-soluble radioactivity in the kidney, plasma, liver, and muscle 24 hr after 1,25-dihydroxycholecalciferol injection has been demonstrated. The present results suggest that, although 1,25-dihydroxycholecalciferol is converted to further metabolites in the rat, it is probably the form of vitamin D responsible for initiating intestinal calcium transport and bone calcium mobilization. (+info)
Direct measurement of osteolysis in man.
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Precise, direct measurement of bone calcium release (v(o-)) has been accomplished using a continuous tracer administration (CTA) technique. Dietary calcium (96.97% (40)Ca) is replaced by (40)Ca (99.991% (40)Ca) and blood levels of the naturally occuring isotope (48)Ca are monitored by neutron activation analysis as a function of time. (48)Ca abundance falls as this isotope is excreted and only partially replaced by release from bone. After a suitable period, an asymptotic abundance of (48)Ca in serum, E, is approached which is the fraction of the turnover rate of the rapidly exchangeable calcium pools coming from the skeleton (E = v(o-)/v(t)). E is determined with a standard error of 2%, providing a precise, sensitive index of v(o-). 13 studies in three normal men and one postmenopausal woman receiving maintenance estrogen show large intersubject variations in parameters of calcium metabolism using both CTA and pulse tracer administration (PTA) plus balance techniques. Induced hypercalcemia results in a prolonged decrease in v(o-). Glucocorticoid therapy initially and consistently induces a marked hypercalciuria while effects on most other parameters of calcium kinetics are variable. In two men E fell when testosterone was added to glucocorticoid treatment, consistent with the known antiosteolytic effect of androgens, despite the short period of study. (+info)