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Biomedical subjects

M Peterlik

Publications and source records attributed to M Peterlik.

At least 73 records · Page 4Linked to original sources
PubMed1989

D-glucose uptake is increased in jejunal brush-border membrane vesicles from hyperthyroid chicks.

Jejunal brush-border membrane vesicles were harvested from 4-week old chicks whose thyroid status had been altered either by a daily injection of 20 micrograms T3 for 1 week or which through the preceding 4 weeks had received propylthiouracil and that had been repleted with either 20 or 80 micrograms T3 in divided doses within 48 h. T3 markedly stimulated D-glucose uptake in brush-border membrane vesicles in the presence of an outside/inside (100/0 mmol/l) Na+ gradient. T3 administration had no detectable influence on the Na+ permeability of the isolated vesicles. The effect of the thyroid hormone on Na+ gradient-driven D-glucose uptake was fully preserved at zero transmembrane potential difference. These findings exclude that T3 stimulates Na+-dependent D-glucose transport in the small intestine through changes of the electrochemical Na+ gradient or through alteration of the transmembrane potential difference. Tracer exchange experiments under equilibrium and voltage-clamp conditions revealed a significantly shorter half-time of D-glucose uptake in brush-border membrane vesicles from T3-treated chicks. Kinetic analysis showed that T3 administration significantly increases the apparent maximal velocity of D-glucose transport in brush-border membrane vesicles, whereas the apparent Km values were virtually unaltered. From these data we conclude that T3 increases the activity of Na+-dependent D-glucose carriers in the brush-border membrane. This is interpreted as consistent with a greater rate of D-glucose absorption from the intestinal lumen under conditions of hyperthyroidism.

Animals↗
PubMed1989

Effect of auranofin on resorption, prostaglandin synthesis and ultrastructure of bone cells in cultured mouse calvaria.

Auranofin (AF) in concentrations between 3 x 10(-7) and 3 x 10(-6) mol/l stimulated bone resorption in cultured neonatal mouse calvariae significantly with 1 x 10(-6) mol/l being most potent. Complete inhibition by 5 x 10(-7) mol/l indomethacin and increased medium concentrations of prostaglandin (PG) E2 and 6-keto-PGF1 alpha after 72 h indicate a PG mediated mechanism. Morphology revealed active osteoclasts. Cytotoxic effects were observed with 3 x 10(-6) and 1 x 10(-5) mol/l AF with osteocytes and osteoblasts being considerably more sensitive than osteoclasts. The latter concentrations inhibited bone resorption stimulated by parathyroid hormone (PTH) 1,25-dihydroxyvitamin D3, PGE2, thrombin and interleukin 1. The stimulatory effect of AF on PG production and subsequent bone resorption could limit its therapeutic usefulness.

Animals↗
PubMed1988

Calcium and inorganic phosphate transport in embryonic chick intestine: triiodothyronine enhances the genomic action of 1,25-dihydroxycholecalciferol.

The influence of triiodothyronine (T3) on the induction of intestinal calcium and inorganic phosphate (Pi) transport by 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) was studied in 48 h cultures of embryonic chick jejunum. While T3 alone had no effect on calcium uptake by gut segments cultured on d 20 of embryonic development, the thyroid hormone amplified the effect of 1,25-(OH)2D3 on calcium transport and effectively shifted the dose-response curve to lower 1,25-(OH)2D3 concentrations. T3 had a dual effect on Pi uptake by cultured jejunum: It induced transport activity even in the absence of the steroid hormone, and, in addition, synergistically raised 1,25-(OH)2D3-related Pi uptake. In d 17 embryonic small intestine, which does not respond to 1,25-(OH)2D3 by a significant increase in Pi transport, T3 permitted the induction of Pi transport by the sterol. In general, the thyroid hormone enhanced the responsiveness of cultured embryonic intestine toward 1,25-(OH)2D3 by two orders of magnitude, resulting in facilitated induction of calcium and Pi transport by the sterol and, in particular, modulated the stage-specific expression of 1,25-(OH)2D3 action on intestinal Pi transport.

Animals↗
PubMed1988

Comparison of the inhibitory effect of nonsteroidal antiinflammatory drugs on bone prostaglandin synthesis and resorption.

The biopotency of various nonsteroidal antiinflammatory drugs (NSAID) in inhibiting prostaglandin (PG) mediated bone resorption was evaluated in a neonatal mouse calvaria organ culture system. Thrombin stimulated formation of the osteolytic PG, PGE2 and PGI2 (measured as 6-keto-PGF1 alpha) and the concomitant stimulation of calcium release from cultured bone were inhibited by diclofenac much greater than indomethacin much greater than flurbiprofen greater than piroxicam greater than acemetacin much greater than acetylsalicylic acid. The relative potencies of the NSAID on PG synthesis in bone differs from that observed previously in other model systems.

Animals↗
PubMed1987

Gamma interferon inhibits basal and interleukin 1-induced prostaglandin production and bone resorption in neonatal mouse calvaria.

Production of the osteolytic arachidonic acid metabolites, prostaglandin (PG) E2, PGI2 and PGF2 alpha, by neonatal mouse calvariae was quantitated by gas chromatography/mass spectrometry. Mouse recombinant interleukin 1 (rIL-1) raised medium levels of PGE2 and PGI2 (measured as 6-keto-PGF1 alpha) in the dose range tested (1.0-10.0 U/ml culture medium), while an effect on PGF2 was only observed at 10 U/ml. Bone resorption in response to rIL-1 reached a plateau at 3.0 U/ml. Mouse recombinant gamma-interferon (rIFN-gamma) between 100-500 U/ml suppressed basal PG synthesis and spontaneous resorption of cultured bone. In addition, IFN-gamma at 100 U/ml prevented stimulation of PG synthesis by 3.0 U/ml rIL-1 and thereby reduced the bone resorbing activity of the cytokine by at least 60%. 5 X 10(-7) M indomethacin was equally effective in suppression of PG synthesis and bone resorption. The present study provides evidence that IFN-gamma inhibits PG synthesis and consequently resorption of cultured bone.

Animals↗
PubMed1987

Calcitriol-dependent, paracellular sodium transport in the embryonic chick intestine.

1,25-Dihydroxyvitamin D3 (calcitriol), or vitamin D3 itself, when added to cultures of 20-day-old embryonic chick small intestine, stimulated sodium (Na+) uptake from the mucosal surface. The calcitriol-mediated increase in Na+ uptake appeared to be related to increased tight-junctional or paracellular permeability. Support for this conclusion was, first, that the uptake of other ions, potassium (K+) and rubidium (Rb+), with tight-junctional permeabilities greater than Na+, was also stimulated by calcitriol, and second, perturbation of cellular Na+ and K+ fluxes by inhibition of Na+/K+-ATPase activity did not affect calcitriol-stimulated Na+, K+, or Rb+ transport. Calcitriol stimulation of Na+ fluxes across the brush border as an alternate possibility is unlikely for the following reason: the calcium ionophore A23187, while mimicking the stimulatory action of calcitriol on calcium (Ca2+) uptake, reduced epithelial Na+ uptake. It is therefore suggested that calcitriol, by virtue of its effect on Ca2+ transport, reduces rather than stimulates cellular Na+ uptake.

Animals↗
PubMed1987

Cyclosporine A inhibits bone resorption in cultured neonatal mouse calvaria.

The effect of the immunosuppressive agent cyclosporine A (CsA) on the resorption of neonatal mouse calvaria was examined in vitro. CsA, at concentrations of 10(-7) to 3 X 10(-5) M, inhibited bone resorption produced by 10(-8) M parathyroid hormone, 3 U/ml of mouse recombinant interleukin-1,5 X 10(-7) M prostaglandin E2, 14 U/ml of thrombin, 5 micrograms/ml of bacterial lipopolysaccharide or 10(-9) M 1 alpha,25-dihydroxyvitamin D3. The effects of CsA on resorption were maintained over 72 h of culture with parathyroid hormone or prostaglandin E2 with no evidence of "escape". Removal of CsA from the cultures resulted in recovery of the resorptive response after a 24-h delay. CsA did not affect thymidine incorporation into DNA in the calvaria. Our results demonstrate that CsA is a nonselective antiresorptive agent in bone, with actions that differ somewhat from those of calcitonin. The results confirm and extend our previous findings on effects of CsA in fetal rat limb bones, with the exception that the inhibitory effects of CsA were more rapidly and completely reversible in the limb bone system.

Animals↗
PubMed1986

Electrical and molecular coupling between sodium and proton fluxes in basolateral membrane vesicles of rat liver.

Mechanisms of Na+-H+ exchange in the hepatocyte were studied utilizing isolated basolateral membrane vesicles prepared by two different methods: Evidence was obtained for the existence of molecular coupling of Na+ and H+ fluxes (Na+/H+-antiport) which exhibits saturation kinetics (Km 7 mmol/l Na+) and is inhibited by amiloride (1.0 mmol/l). Although the two membrane preparations showed differences with respect to ionic permeabilities, our data suggest that a relatively high H+ conductance exists in the basolateral plasma membrane. Hence, electrical coupling of conductive H+ and Na+ fluxes in the opposite direction could contribute to net Na+-H+ exchange across the basolateral hepatocyte plasma membrane.

Animals↗
PubMed1986

Indomethacin inhibits thrombin-, but not thyroxin-stimulated resorption of fetal rat limb bones.

The bone-resorbing effects of thrombin and thyroxin, two agents that stimulate resorption in neonatal mouse calvaria by prostaglandin-dependent mechanisms, were examined in cultures of fetal rat limb bones. Thrombin produced maximal resorption in the limb bone cultures at a concentration of 100 U/ml when bones were cultured in BGJ supplemented with 1 mg/ml bovine serum albumin. The effects of thrombin were partially inhibited by 0.5 and 10 uM indomethacin. Thrombin failed to elicit resorption when the limb bones were cultured in DMEM with 15% horse serum. Thyroxin stimulated the resorption of limb bones in both BGJ-albumin and DMEM-serum media. Resorption was elicited by thyroxin concentrations of 10 nM-10 uM. 30 uM thyroxin failed to stimulate resorption. The dose-response curve to thyroxin was shallow, and the agent did not produce maximal resorption. The bone-resorbing effects of thyroxin were not affected by 0.5 or 10 uM indomethacin.

Animals↗
PubMed1986

Intestinal phosphate and calcium absorption: joint regulation by thyroid hormones and 1,25-dihydroxyvitamin D3.

Thyroxine (T4) and triiodothyronine (T3) activate Na+-dependent inorganic phosphate (Pi) transport in organ-cultured embryonic chick small intestine. Induction of transport activity requires intact protein synthesis and can be expressed in enterocytes with varying degrees of differentiation. T3 and T4 exert their effect independent of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is shown to stimulate Pi uptake only in the final stage of embryonic differentiation. At this time point, a potentiating effect of 1,25(OH)2D3 and T4 on Pi transport in cultured jejunum can be demonstrated. Thyroid hormones appear to stimulate Na+ gradient-driven Pi transport without concomitantly raising (Na+-K+)-ATPase activity. T4 has no influence whatsoever on calcium uptake by cultured embryonic small intestine while 1,25(OH)2D3 is effective at all stages of embryonic development investigated (day 15-20). However, when both hormones were present in the culture medium, the effect of 1,25(OH)2D3 on calcium transport is doubled. Our results suggest that the hyperphosphataemia associated with hyperthyroidism is likely to result, at least in part, from the independent effect of thyroid hormones as well as from their potentiation of the 1,25(OH)2D3 action on Na+-dependent intestinal Pi transport. In addition, their permissive effect on 1,25(OH)2D3-induced calcium absorption provides an explanation for unaltered calcium absorption in a number of hyperthyroid patients, although reduced plasma levels of 1,25(OH)2D3 are generally observed in this condition.

Animals↗
PubMed1985

Effects of 1 alpha,25-dihydroxycholecalciferol on sodium-ion translocation across chick intestinal brush-border membrane.

By utilizing isolated brush-border vesicles, Na+ transport across the luminal membrane of chick small intestine was found to be a composite of (i) a saturable (Km 10mM-Na+) amiloride-sensitive Na+/H+ antiport and (ii) a potential-sensitive conductive pathway. No evidence was obtained for the existence of a Na+/Cl- symport system. With the exception of the duodenum, luminal Na+ transfer in the entire small intestine was subject to regulation by vitamin D. Repletion of vitamin D-deficient chicks with 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3] significantly decreased net Na+ uptake by isolated membrane vesicles (by approximately 30%). The sterol suppresses the conductive pathway (25-45% inhibition) as well as the Na+/H+ antiport system. Kinetic analysis of the latter revealed that 1 alpha,25(OH)2D3 altered Vmax (from 12.9 to 4.8 nmol of Na+/20s per mg of protein), but did not change Km. Diminution of Na+ transfer, entailing an increase in the electrochemical transmembrane Na+ gradient, provides an explanation of the simultaneously observed stimulatory action of 1 alpha,25(OH)2D3 on Na+-gradient-driven solute transport in chick small intestine. Indirect evidence was obtained that the luminal plasma membrane of chick small intestine displays a definite H+ permeability that is positively affected by 1 alpha,25(OH)2D3.

Amiloride↗
PubMed1985

Recombinant gamma-interferon inhibits prostaglandin-mediated and parathyroid hormone-induced bone resorption in cultured neonatal mouse calvaria.

A role of gamma-interferon in the bone remodeling process can be implicated from its interference with bone resorptive processes in cultured neonatal mouse calvaria. The immune interferon is an efficient inhibitor of endogenous prostaglandin synthesis, particularly after stimulation by thrombin or arachidonic acid, and, in addition, has a calcitonin-like inhibitory effect on PTH-induced osteoclastic bone resorption.

Animals↗
PubMed1985

Prostaglandin-related bone resorption in cultured neonatal mouse calvaria: evaluation of biopotency of nonsteroidal anti-inflammatory drugs.

The objective of this study was the development of an assay based on suppression of endogenous prostaglandin synthesis in cultured neonatal mouse calvaria for evaluation of the biopotency of nonsteroidal anti-inflammatory drugs in bone. In preliminary trials, osteolytic activity due to spontaneous prostaglandin production over a 72 h culture period was found highly variable, and could not be stabilized by addition of the common precursor arachidonic acid to the culture medium. Eventually, continuous exposure of mouse calvaria to moderate concentrations of thrombin (greater than or equal to 14 U/ml medium) proved to be satisfactory to achieve stable rates of bone resorption through continuous stimulation of prostaglandin synthesis from endogenous sources. Notably, the extent of net calcium release into the medium was highly reproducible in different experiments. As an example for possible applications of the bioassay, the ability of acemetacin to interfere with prostaglandin synthesis in bone, which had not been assessed before, was evaluated in a comparative assay with indomethacin and acetylsalicylic acid. While 1 X 10(-8) M acemetacin appeared to augment thrombin-induced bone resorption, as did 5 X 10(-6) M acetylsalicylic acid, a dose-dependent inhibition of calcium release was observed between 10(-7)-10(-5) M acemetacin. In this respect, the biopotency of indomethacin was 50 times higher than that of acemetacin and exceeded that of acetylsalicylic acid by a factor of more than 2000. These data could be useful for the appraisal of multiple effects of the investigated drugs on prostaglandin-related bone turnover.

Animals↗