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Biomedical subjects

R Beitner

Publications and source records attributed to R Beitner.

At least 19 recordsLinked to original sources
PubMed1992

Insulin rapidly stimulates binding of phosphofructokinase and aldolase to muscle cytoskeleton.

1. We report here on a novel action of insulin which shows that the hormone stimulates binding of phosphofructokinase (PFK) and aldolase to muscle cytoskeleton. 2. This effect was demonstrated both in vivo, by injection of insulin, in the tibialis anterior and gastrocnemius muscles, as well as in vitro, in the isolated rat diaphragm muscle incubated with insulin. 3. Insulin exerted this effect at physiologic range of concentrations and very rapidly (about 50% stimulation of binding occurred within 1 min). 4. The possible physiological significance of this rapid action of insulin, is to provide local ATP, generated by the accelerated cytoskeletal glycolysis, for other rapidly insulin-stimulated membrane-cytoskeleton processes.

Animals↗
PubMed1992

Sequence of insulin effects on cytoskeletal and cytosolic phosphofructokinase, mitochondrial hexokinase, glucose 1,6-bisphosphate and fructose 2,6-bisphosphate levels, and the antagonistic action of calmodulin inhibitors, in diaphragm muscle.

1. Time-curves of insulin effects on energy-producing systems in different cellular compartments of rat diaphragm muscle have revealed: (a) a rapid (within minutes) and transient stimulatory effect of insulin on cytoskeletal phosphofructokinase and aldolase and mitochondrial hexokinase. (b) A slower and consistent stimulatory effect on glucose 1,6-bisphosphate level, with concomitant gradual activation of cytosolic phosphofructokinase. Fructose 2,6-bisphosphate levels were not changed by insulin. (c) Lactate concentration correlated with the stimulation of cytoskeletal and cytosolic glycolysis. 2. Calmodulin antagonists, trifluoperazine or CGS 9343B, prevented all these effects of insulin. 3. These results suggest that cytoskeletal glycolysis and mitochondrial oxidation are the source of ATP for the rapid actions of insulin, whereas cytosolic glycolysis is the source of ATP for the slow actions of insulin. Calmodulin is involved in all these effects of insulin.

Animals↗
PubMed1992

Ca(2+)-ionophore A23187 and the Ca(2+)-mobilizing hormones serotonin, vasopressin, and bradykinin increase mitochondrially bound hexokinase in muscle.

We show that a rise in cytosolic-free Ca2+ in muscle, induced by Ca(2+)-ionophore A23187 or by the Ca(2+)-mobilizing hormones serotonin, vasopressin, and bradykinin, increases the binding of hexokinase to mitochondria in muscle. This increase could be prevented by treatment with the calmodulin antagonists trifluoperazine or CGS 9343B (a novel, potent, and selective inhibitor of calmodulin activity) which strongly suggests that calmodulin is involved in the Ca(2+)-induced binding of the enzyme to muscle mitochondria.

Animals↗
PubMed1991

Effect of the calmodulin antagonist CGS 9343B on skin burns.

1. CGS 9343B is a novel, potent and selective inhibitor of calmodulin activity, which unlike other known calmodulin antagonists, does not inhibit protein kinase C activity and does not possess potential antidopaminergic activity. Here we show that CGS 9343B, like other calmodulin antagonists reported previously, is most effective in treatment of burns. 2. The effectiveness of CGS 9343B on skin burns was evaluated by electron microscopic studies, as well as by measurements of hemoglobin, ATP and enzymes which are markedly changed in the burned skin. 3. As CGS 9343B is a more selective probe for calmodulin function than other inhibitors, the similarity of its effects on burns to that of other calmodulin antagonists, strongly suggest that their action on burns is mediated through calmodulin inhibition.

Adenosine Triphosphate↗
PubMed1991

Altered allosteric properties of cytoskeleton-bound phosphofructokinase in muscle from mice with X chromosome-linked muscular dystrophy (mdx).

Intracellular distribution of cytoskeleton-bound and soluble phosphofructokinase (PFK) (the rate-limiting enzyme in glycolysis) in mdx dystrophic muscle was the same as in control nondystrophic muscle. However, the allosteric activity of both bound and soluble PFK was reduced in mdx muscle, accompanied by a decrease in ATP level. In contrast to normal muscle, the cytoskeleton-bound PFK in mdx muscle was sensitive to allosteric regulation, like the soluble enzyme. This change in the properties of cytoskeletal PFK in mdx mice may result from the absence of dystrophin, believed to reside in the cytoskeleton. The findings that cytoskeletal PFK in mdx muscle, although altered, remains bound to cytoskeleton may play a role in muscle structure and function and the mild clinical symptoms in mdx mice.

Adenosine Triphosphate↗
PubMed1990

Decrease in cytoskeleton-bound phosphofructokinase in muscle induced by high intracellular calcium, serotonin and phospholipase A2 in vivo.

1. Particulate (cytoskeleton-bound) and soluble phosphofructokinase (PFK), separated from rat muscle, exhibited different allosteric properties; in contrast to the soluble PFK, the bound enzyme was not sensitive to allosteric regulation. 2. Treatment of muscle with Ca2(+)-ionophore A23187, serotonin, or phospholipase A2, reduced the binding of PFK and aldolase. 3. The decrease in enzymes' binding was most probably mediated by the rise in free intracellular Ca2+ induced by these agents, as we found that direct addition of Ca2+ to the particulate fraction of muscle, caused solubilization of bound PFK and aldolase. 4. The reduction in binding of PFK and aldolase to cytoskeletal proteins, may have a deleterious effect on muscle function and structure, and may be involved in the mechanism of muscle damage in pathological conditions where accumulation of Ca2+ occurs.

Animals↗
PubMed1989

Effects of epinephrine on glucose-1,6-bisphosphate and carbohydrate metabolism in skin.

1. Injection of epinephrine induced in skin a decrease in the level of glucose-1,6-bisphosphate (Glc-1,6-P2), which was accompanied by correlated changes in the activities of several enzymes which are modulated by this regulator. 2. These effects were blocked by the alpha adrenergic blocker phentolamine, in contrast to muscle where the hormone increases Glc-1,6-P2, acting through beta receptors. 3. The changes in the enzymes' activities, as well as in glycogen and lactate content induced by epinephrine, reveal that the hormone causes, in skin, a stimulation of glycogenolysis and glycolysis, as well as an acceleration of pentose phosphate pathway. 4. The reduction in glycogen content induced by epinephrine, was blocked by the beta adrenergic blocker propranolol, whereas the hormone's effects on the other processes were mainly mediated through alpha receptors.

Adenosine Triphosphate↗
PubMed1989

Therapeutic and prophylactic treatment of skin burns with several calmodulin antagonists.

1. Several calmodulin antagonists abolished the decrease in ATP level and in the activities of 6-phosphogluconate dehydrogenase and mitochondrial and soluble hexokinase, induced by burns in the rat skin. 2. These antagonists had also a protective action on the blood capillaries and erythrocyte membrane, as judged by the electron microscopic appearance, as well as the abolishment of hemoglobin increase and burn edema. 3. Of all the compounds investigated here, the most effective were trifluoperazine and thioridazine, which are also known as the more potent calmodulin antagonists. 4. The present experiments suggest that calmodulin antagonists may be effective drugs in treatment of burns, having both therapeutic and prophylactic action.

Adenosine Triphosphate↗
PubMed1989

Treatment of frostbite with the calmodulin antagonists thioridazine and trifluoperazine.

1. Thioridazine and trifluoperazine, which have been previously found in this laboratory to be the most effective calmodulin antagonists in treatment of burns, are shown here to be also effective in the treatment of frostbite. 2. Electron microscopic studies have revealed a complete reversal of both the vascular and skin tissue damage induced by frostbite. 3. The reversal of the vascular damage was also demonstrated by the ability of these compounds to abolish the increase in hemoglobin content in the skin. 4. The reversal of the skin tissue damage was also revealed by the ability of these compounds to raise the decreased ATP level and the reduced activities of 6-phosphogluconate dehydrogenase and mitochondrial and soluble hexokinase in skin, induced by frostbite, to normal control levels.

Adenosine Triphosphate↗
PubMed1987

Exogenous ATP antagonizes the actions of phospholipase A2, local anesthetics, Ca2+ ionophore A23187, and lithium on glucose-1,6-bisphosphate levels and the activities of phosphofructokinase and phosphoglucomutase in rat muscle.

ATP, added externally to the incubation medium of rat diaphragm muscles, abolished the decrease in the levels of glucose-1,6-bisphosphate (Glc-1,6-P2), the powerful regulator of carbohydrate metabolism, induced by phospholipase A2, local anesthetics, Ca2+ ionophore A23187, or lithium. Concomitantly to the changes in Glc-1,6-P2, the potent activator of phosphofructokinase (the rate-limiting enzyme in glycolysis) and phosphoglucomutase, the activities of these enzymes were reduced by the myotoxic agents and restored by exogenous ATP, when assayed under conditions in which these enzymes are sensitive to regulation by Glc-1,6-P2. These findings suggest that ATP may have broad therapeutic action, as it may stimulate the impaired glycolysis in muscle induced by various drugs and conditions which cause muscle weakness or damage.

Adenosine Triphosphate↗
PubMed1985

Trifluoperazine abolishes the actions of bradykinin on glucose 1,6-bisphosphate levels and on the activities of glucose 1,6-bisphosphatase, phosphofructokinase and phosphoglucomutase.

Injection of trifluoperazine abolished the bradykinin-induced decrease in intracellular concentration of glucose 1,6-bisphosphate (Glc-1,6-P2) in rat tibialis anterior muscle and skin. These changes in Glc-1,6-P2 levels may be attributed to the changes in the activity of glucose 1,6-bisphosphatase (the enzyme that degrades Glc-1,6-P2), which was markedly enhanced by bradykinin and reversed by trifluoperazine. Concomitantly to the changes in Glc-1,6-P2, the potent activator of phosphofructokinase and phosphoglucomutase, the activities of these enzymes were reduced by bradykinin and restored by trifluoperazine. These findings suggest that trifluoperazine treatment may have a beneficial effect on the depressed glycolysis induced by bradykinin in tissue damage.

Animals↗
PubMed1979

Inhibition of 6-phosphogluconate dehydrogenase (decarboxylating) by glucose 1,6-bisphosphate.

Glucose 1,6-bisphosphate, the powerful common regulator of several key enzymes in carbohydrate metabolism, was found to exert a potent inhibitory effect on the activity of 6-phosphogluconate dehydrogenase (decarboxylating) from yeast and several rat tissues. These findings suggest that glucose 1,6-bisphosphate may have a regulatory influence on the pentose phosphate pathway.

Animals↗
PubMed1978

The levels of cyclic GMP and glucose 1,6-diphosphate, and the activity of phosphofructokinase, in muscle from normal and dystrophic mice.

A striking reduction in the levels of glucose 1,6-diphosphate and an increase in cyclic GMP were found in muscle from dystrophic mice. Concomitant to these changes, the allosteric activity of phosphofructokinase was found to be markedly reduced. These findings could offer an explanation for the observed reduction in glycolysis in the dystrophic muscle.

Allosteric Regulation↗