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Biomedical subjects

F Bronner

Publications and source records attributed to F Bronner.

At least 19 recordsLinked to original sources
PubMed1992

Modulation of bone calcium-binding sites regulates plasma calcium: an hypothesis.

A new model of calcium (Ca) homeostasis is proposed. It is based on the kinetics of restoration of the plasma Ca level following positive or negative Ca loads in animals of different endocrine status. As others, we can account for the kinetics of plasma Ca restoration as being the result of a very rapid dilution of Ca into extracellular water (t1/2 less than 1 minute) and an uptake or release by bone (t1/2 = 14-80 minutes) that occurs as the fraction of cardiac output directed to bone is partially cleared of or repleted with Ca. In this model, bone surfaces have Ca-binding sites that demonstrate a range of affinities and whose average Km determines the plasma Ca level. Acute regulation is brought about by controlling access to subpopulations of Ca binding sites in bone, comprising the extremes of high and low affinity. Osteoblasts, when active and extended, block the low affinity sites, and osteoclasts, when active and extended, block the high affinity sites. Exposure of low- or high-affinity sites is brought about when these cells respond to hormonal signals by contraction, parathyroid hormone (PTH), and vitamin D leading to osteoblast, and calcitonin to osteoclast, contraction. These reciprocal cell shape changes are the first in a cascade of metabolic events that lead to bone formation and resorption, as well as changes in the number or affinity of the binding sites. The model also accounts for the prolongation of the response time to Ca loads in animals deprived of PTH, calcitonin, or vitamin D.

Animals↗
PubMed1992

Net calcium absorption in premature infants: results of 103 metabolic balance studies.

Net calcium absorption was evaluated in 103 low-birth-weight preterm infants by a 72-h balance technique. At birth the infants had a mean (+/- SE) gestational age of 30.9 +/- 0.2 wk and weighed 1.43 +/- 0.03 kg. When tested 3 wk later, their net calcium absorption averaged 58 +/- 1% with an intake of 80 +/- 2 mg Ca.kg body wt-1.d-1. Of the 103 infants, 58 had been fed low-birth-weight formulas supplemented with vitamin D. The remainder received banked human milk, of whom 34 were supplemented with vitamin D and calcium; 11 infants received no supplementation. Calcium absorption in the four subgroups did not differ significantly, with neither vitamin D supplementation nor supplementation with vitamin D and calcium affecting percent absorption significantly. Net calcium absorption was a linear function of intake (40-130 mg Ca.kg body wt-1.d-1) with a zero intercept. Because vitamin D supplementation did not increase net calcium absorption, it is concluded that in preterm low-birth-weight infants calcium absorption proceeds by a nonsaturable route, with the transcellular, vitamin D-regulated mechanism not yet expressed.

Calcium↗
PubMed1992

Bone and calcium homeostasis.

The principal repository of calcium is bone. Calcium enters bone largely via the trabeculae, with the rate of calcium clearance by bone approximating 50 percent. Calcium enters bone as an ion in solution, but undergoes a phase change to a solid as soon as in contact with the bone surfaces. Calcium removal from and redistribution in bone is mediated by the bone cells, principally osteoblasts and osteoclasts. Calcium enters the body via intestinal absorption, a transport process that is the vectorial result of a saturable and an non-saturable step. Calcium leaves the body in the urine and stool, with a circulating calcium ion having one chance in about four of being lost via excretion. Ions like lead can compete with calcium at the sites of calcium deposition and transport. Their rate in the body should therefore parallel that of calcium, but may be modified by differing binding affinities or interactions with specific sites and molecules.

Animals↗
PubMed1992

Microdistribution of lead in bone: a new approach.

A knowledge of the microdistribution of lead in bone is important in order to understand the mechanisms for accumulation and release of lead. The availability of the synchrotron x-ray microscope for sensitive measurements of bone content and distribution of lead provides a valuable tool which, when combined with kinetic, balance, and tissue measurements, can lead to better evaluation of lead toxicity. It may also provide the basis for the development of a suitable model of how lead behaves in the human body. An outline of an experimental protocol for exploitation of the x-ray microscope is given, along with synchrotron x-ray microscope measurements of the distribution of gallium in rat bone that demonstrate the feasibility of the experimental approach.

Animals↗
PubMed1991

A human periodontal ligament fibroblast clone releases a bone resorption inhibition factor in vitro.

The conditioned media (CM) obtained from three lines of cloned human periodontal ligament (PDL) cells were analyzed to determine whether they altered the parathyroid hormone (PTH)-stimulated resorption rates (45Ca release) in 48-hour cultures of 45Ca-labeled rat long bones. One PDL cell line, PDL-5, produced a heat-resistant factor in its CM that inhibited the PTH-stimulated resorption by 43.8 +/- 9.7 (SE) percent (p less than or equal to 0.02), whereas the CM from the other cell lines were without statistically significant effect. The CM from the PDL-5 line did not diminish organ culture viability, as determined by 3H-thymidine incorporation, and did not enhance or diminish the resorption-inhibiting activity of calcitonin added to the PTH-stimulated cultures. The addition of CM from PDL-5 did not alter the bone-resorbing effect of interleukin-1 (IL-1). These results indicate that CM from PDL-5 inhibits only the PTH-induced and not the IL-1-mediated resorption processes, whose mechanisms are therefore likely to differ.

Analysis of Variance↗
PubMed1990

Intestinal calcium transport: the cellular pathway.

The active calcium transport process in the intestine is transcellular. Entry across the brush border of the enterocyte is down an electrochemical gradient, probably via calcium channels. The entry process, although modified by vitamin D, does not appear to be the rate-limiting step, as total vitamin D deficiency lowers the rate of entry only by about a third, whereas active calcium transport is wholly inhibited. Calcium extrusion is effected by the Ca-ATPase, is against an electrochemical gradient, and requires a supply of energy. However, it is not the rate-limiting step, as extrusion capacity is more than sufficient to handle the maximum transcellular flux of calcium. It is the flow of calcium inside the cell, from the brush-border pole to the pump at the basolateral side, that is rate-limiting. Basal calcium flow, in the absence of the cytosolic, vitamin D-dependent calcium-binding protein, CaBP, is only about 1/70 of the maximum rate, Vm, in the vitamin D-replete duodenum. CaBP levels vary linearly with the Vm. Moreover, interference with calcium binding by CaBP interferes with active calcium transport. Active calcium transport is totally regulated by vitamin D or processes that modify the action or metabolism of the sterol. Since, however, active calcium transport is only one of the two routes of calcium absorption, the other being a passive, paracellular process, up- or down-regulation of active transport may have only a limited effect on total calcium absorption.

Animals↗
PubMed1989

Acute plasma calcium regulation in rats: effect of vitamin D deficiency.

Vitamin D-replete (+D) and vitamin D-deficient (-D) rats received large doses of calcium (2-18 mg) by intraperitoneal injection and their responses to the calcium load was analysed in terms of the instantaneous and time-dependent responses of the plasma calcium concentration, [Cas]. Following an initial expansion, [Cas] returned to the preinjection value in a strictly exponential manner, with t1/2 = 22.5 +/- 2.0 (SE) min in +D and 51 +/- 5.2 min in -D animals. In both groups of animals, these rates were independent of the calcium load. Extraprolation of [Cas] to t = 0, i.e., the time just after administration of the calcium, revealed that the amount of calcium circulating at that moment was only about one-fifth of the amount that would have been found if all of the injected calcium had remained in the plasma. Calculations suggest that in all animals about four-fifths of the injected calcium load became distributed virtually instantaneously in the extracellular water. In both +D and -D groups the fraction of the injected load that left the plasma instantaneously was independent of the calcium load, of [Cas] at t = 0 or of the animals' plasma volume. The ability of rats to disperse some 80% of the load to outside the plasma would seem to constitute a major mechanism of acute plasma calcium regulation. Dilution was insufficient, however, totally to reduce [Cas] to the preinjection level. That occurred exponentially, with most of the calcium presumed to enter the skeleton. This exponential rate was markedly and significantly slower in the vitamin D-deficient animals than in their controls.

Animals↗
PubMed1989

Theophylline inhibits transcellular Ca transport in intestine and Ca binding by CaBP.

Theophylline, when added to the incubation medium of everted duodenal sacs prepared from rats on a low-calcium diet, was found to inhibit transcellular Ca transport in a concentration-dependent manner, with an inhibitor constant (Ki) of 10.8 mM theophylline. Neither the rate of cellular Ca entry, as evaluated with the aid of brush-border membrane vesicles, nor the rate of cellular Ca extrusion, assessed by measuring ATP-dependent Ca uptake of basolateral membrane vesicles, was significantly altered by the addition of theophylline to the uptake media. However, Ca-binding by calcium-binding protein (CaBP; calbindin D9k), Mr approximately 8,800) was depressed by theophylline in a concentration-dependent manner, with Ki = 3.2 mM theophylline. Theophylline had no effect on Ca binding by calmodulin and the theophylline-induced inhibition of transcellular calcium transport was independent of adenosine 3',5'-cyclic monophosphate levels. Theophylline also had no effect on paracellular Ca movement. Since the theophylline-induced inhibition of Ca-binding by CaBP paralleled the inhibition of transcellular Ca transport, it is concluded that CaBP functions in transcellular Ca transport via its ability to bind Ca.

Animals↗
PubMed1989

Renal calcium transport: mechanisms and regulation--an overview.

Renal calcium transport is described as the result of two processes, a paracellular, gradient-dependent process that predominates in most segments of the nephron and a transcellular, energy-dependent step that characterizes calcium transport in the distal convoluted tubule (DCT). Transcellular calcium transport involves entry into the DCT cell, possibly via channels, intracellular movement which appears to be facilitated by the presence of the vitamin D-dependent, cytosolic calcium-binding protein (CaBPr, calbindin D28k, mol mass approximately 28 kDa), and extrusion via the Ca-ATPase. Although much is known about calcium channels, their presence in renal tissue has only been demonstrated by preliminary studies. Quantitative data on CaBPr content of rat DCT are also unavailable, but theoretical analysis and early experimental values of intracellular self-diffusion of calcium have confirmed the need for an intracellular calcium "ferry," i.e., a molecule like CaBPr to amplify intracellular calcium movement. Available data on the plasma membrane Ca-ATPase are consistent with the extrusion kinetics attributed to the renal Ca-ATPase, but it has not been isolated, nor has its gene been cloned. Regulation and disorders of renal calcium transport are likely to involve one of the three transcellular steps, but indirect regulation by modification of the cell walls and molecules constituting the paracellular pathway cannot be excluded.

Animals↗
PubMed1988

Vitamin D-dependent active calcium transport: the role of CaBP.

Transepithelial calcium transport in the intestine involves an active and a passive route. The active route is totally vitamin D-dependent, transcellular, and is largely expressed in the proximal intestine. Of the three steps involved in transcellular transport--entry into the mucosal cell, intracellular movement, and extrusion at the basolateral pole of the cell--neither entry nor extrusion appears rate-limiting in the absence of vitamin D, even though both are enhanced as a result of the action of the vitamin D. However, intracellular calcium movement inside the mucosal cell can match the experimental Vm of transcellular transport only in the presence of the vitamin D-dependent calcium-binding protein (CaBP, Mr = 8.8kDa). CaBP is thought to act as the equivalent of a calcium ferry by amplifying the intracellular movement of calcium. Thus, the major action of vitamin D on cellular calcium transport is via its hormonal product, CaBP, which amplifies intracellular calcium movement by raising total and free calcium levels in the transporting cell.

Animals↗
PubMed1988

CaBPr facilitates intracellular diffusion for Ca pumping in distal convoluted tubule.

The system of renal Ca transport in the rat is modeled in terms of two classes of processes: a nonsaturable flux that predominates in the proximal tubule, and an active, vitamin D-dependent flux with major expression in the distal convoluted tubule. There transport is against an electrochemical gradient, with much of the efflux probably mediated by the Ca/Mg-ATPase. Calculations of the rate of free Ca diffusion in tubular cells indicate that an unaided flux would be only one-seventy-seventh of that found experimentally. It is suggested that the vitamin D-induced renal calcium binding protein, CaBPr, Mr approximately 28,000, in raising total cellular calcium by three orders of magnitude, increases the transcellular Ca flux and thus the free intracellular Ca ion concentration at the basolateral pole, allowing the Ca/Mg-ATPase to function near its maximum. Analysis of the rate of nonsaturable Ca flux throughout the kidney tubule suggests a paracellular pathway via bulk flow, following water that is driven osmotically. Evaluation of whole animal data in terms of these two classes of calcium fluxes indicates that our model is consistent with experimental observations and assigns a functional role to active calcium transport.

Animals↗
PubMed1987

Intestinal calcium absorption: mechanisms and applications.

Calcium absorption from the intestine involves two sets of events. One, a saturable transcellular process is regulated by vitamin D via its molecular product, the calcium-binding protein (CaBP, MW = 8800). This transcellular movement is largely confined to the proximal portion of the intestine. The second process is nonsaturable, occurs throughout the length of the intestine and is paracellular. Evidence in support of these statements is discussed, with emphasis on kinetic considerations. It is proposed that CaBP acts as a ferry, amplifying the intracellular movement of calcium by a factor of about 60, thereby enabling transcellular calcium transport to reach the measured values of Vm = 22 mumol/h per gram (wet) duodenum, with Km = 3.9 mM. The transcellular process is subject to down-regulation and is influenced by functional or nutritional factors such as age or calcium intake. The nonsaturable process, on the other hand, is not directly influenced by these or related events. Vitamin D therapy alters active calcium transport, but may lead to undesirable effects at other target organs, e.g., kidney or bone. An increase in calcium intake is the simplest method for increasing the amount absorbed. Future research may show whether paracellular pathway alterations are a practical approach to changing the amount of calcium absorbed by the nonsaturable process.

Animals↗