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Organic phosphorus compounds. 2. Synthesis and coronary vasodilator activity of (benzothiazolylbenzyl) phosphonate derivatives.

Structural modification and the coronary vasodilator activity of the calcium antagonist fostedil (KB-944) are described. Elimination of the bezothiazole ring or replacement of the benzothiazole ring of fostedil with other hetero rings leads to a decrease in vasodilator activity. Change of the distance from the aromatic ring to the phosphorus of fostedil causes a decrease in the activity. The present study indicates that the presence of an aromatic ring substituted thiazole ring and the presence of phosphonate at an appropriate distance from the thiazole ring are important for the coronary vasodilator action of fostedil.

Allosteric Site↗

Phosphorus compounds in translocating Phloem.

Phosphate-(32)P was introduced into a turnip leaf, and 3 hr later, the vascular bundles were stripped from the petiole and their phosphate ester pattern was studied. The pattern did not alter along their length and was like that of other tissues. Pumpkin leaves were painted with phosphate-(32)P; and later, the petioles were cut, the sieve tube exudates were collected and their phosphate ester patterns were studied. Exudates collected after 10 min had a high proportion of their (32)P present in P(i) and nucleoside triphosphates, while exudates collected after long translocation times (4-22 hr) had a lower proportion in these, and a higher proportion in hexose monophosphates and UDP glucose. In general, the ester patterns were like those of other tissues. The results indicate that sieve tubes are metabolically active, and that P(i) is the primary form in which phosphorus moves in the phloem.

Journal Article↗

Nature and origins of phosphorus compounds in isolated cell walls of Staphylococcus aureus.

Preparations of purified cell walls from Staphylococcus aureus were shown to contain small amounts of phospholipid and glycerol teichoic acid. Since these are components of the cell membrane, it is probable that the wall itself contains no lipid, but does retain fragments of membrane because of physical connections between wall and membrane. In walls of S. aureus strain 52A5, which completely lacks ribitol teichoic acid, the only phosphorylated compound identified as a genuine wall component was a phosphorylated derivative of murein that gave rise to muramic acid phosphate on acid hydrolysis. Muramic acid phosphate was also identified in hydrolysates of walls from S. aureus H and strain 52A2.

Acyltransferases↗

High molecular weight phosphorus compound in nucleic acid extracts of the slime mold Physarum polycephalum.

Orthophosphate labeled with (32)P was added to the growth medium of the plasmodia of Physarum polycephalum. The nucleic acid extracts of such plasmodia contained (32)P that was not removed by nuclease, protease, or amylase. This labeled material was shown to be separable from nucleic acids, could be eluted from a methylated albumin-kieselguhr column at 0.5 m NaCl, was of high molecular weight, and had several characteristics in common with polyphosphate. A fraction of this polyphosphate-like material was also found in extracts of isolated nuclei.

Molecular Weight↗

Compartment syndrome: a quantitative study of high-energy phosphorus compounds using 31P-magnetic resonance spectroscopy.

The purpose of this study was to quantitate the intracellular high-energy phosphate compounds during 6 hours of tissue ischemia in the anterior tibial compartment of beagles subjected to an induced traumatized compartment syndrome. The goal of this work was to provide clinicians with objective criteria to augment clinical judgment regarding surgical intervention in the impending compartment syndrome. A beagle model was utilized in which the Delta pressure (difference between the mean arterial pressure and compartment pressure) could be controlled. The model, in conjunction with 31P-magnetic resonance spectroscopy (MRS), allowed a measure of high-energy phosphate compounds and pH in the compartment at various Delta pressures. The extent of ischemic metabolic insult in the compartment was then quantitated. Our data suggest the following: 1) lower Delta pressures result in a proportionally greater drop in the intracellular phosphocreatine ratio and pH; 2) at lower Delta pressures, there is proportionally greater decline in the percentage recovery post-fasciotomy; 3) blood pressure is extremely important and periods of hypotension may result in increased muscle damage at lower compartment pressures.

Animals↗

The turnover of phosphorus compounds in crab muscle fibres.

1. The exchange of 32P injected into single crab muscle fibres as either orthophosphate or ATP has been studied. The results have been analysed in terms of a simple kinetic model. 2. The exchange of 32P between ATP and arginine phosphate is considerably faster than that between ATP and orthophosphate during rest and during contraction in caffeine. 3. The rate constants obtained at rest after the injection of either orthophosphate or ATP labelled with 32P were of the same order. They were also of the same order as those which have been obtained previously for squid axons. 4. The exchange during caffeine contraction of 32P unjected as orthophosphate gave rate constants which were consistent with an increased rate of splitting of ATP and with the rate constants needed to account for the observed net formation of orthophosphate. The results obtained after the injection of 32P-labelled ATP during caffeine contraction were less clear cut.

Adenosine Triphosphate↗

Assessment of high-energy phosphorus compounds in the rat kidney by in situ 31P nuclear magnetic resonance spectroscopy: effect of ischemia and furosemide.

31P nuclear magnetic resonance (NMR) spectroscopy of the in situ rat kidney was performed by a surface coil method, and the effects of ischemia and furosemide infusion were assessed. 31P NMR spectra of the kidney subjected to 30 min of ischemia returned completely to the pre-ischemic level after 60 min of reperfusion. But the 31P NMR spectra after 60 min of ischemia did not recover, even after 120 min of reperfusion. Levels of beta-ATP and inorganic phosphate (Pi) decreased and the chemical shift of Pi increased after intravenous infusion of furosemide. This increase in chemical shift might signal an alkalotic change in intracellular pH. Furosemide infusion prior to ischemia is thought to protect the kidney from injury induced by 60 min of warm ischemia. The chemical shift of Pi returned to the pre-ischemic level earlier than beta-ATP and Pi. In conclusion, according to the findings of 31P NMR spectroscopy, furosemide infusion prior to ischemia may be effective in protecting the kidney against ischemic injury. But the change in Pi peak and the causes of the dissociation of Pi and beta-ATP should be examined further.

Animals↗

Organic phosphorus compounds--nerve agents.

The organic phosphorous compounds (OPC) include both the military grade nerve agents and the organic phosphorous pesticides. The major mechanism of OPC toxicity is through inhibition of acetylcholinesterase in neuronal synapses leading to excess acetylcholine and overstimulation of target organs. Signs and symptoms depend on the affinity of the OPC for muscarinic versus nicotinic receptors, and are likely to include both. Muscarinic symptoms may include diarrhea, urination, bronchospasm, bronchorrhea, emesis, and salivation. Nicotinic symptoms such as paralysis and fasciculations may also occur. Central nervous system toxicity may include seizures, altered mental status, and apnea, and require prompt intervention. Treatment includes early airway and ventilatory support as well as antidotal therapy with atropine, pralidoxime, and diazepam. Goals of therapy include prevention and rapid treatment of hypoxia and seizures, as these are linked to patient outcome.

Antidotes↗