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G K Radda

Publications and source records attributed to G K Radda.

At least 343 records · Page 19Linked to original sources
PubMed1980

Localization of metabolites in animals using 31P topical magnetic resonance.

High-resolution phosphorous (31P)-NMR spectra of biological molecules provide detailed information about the metabolism of living systems. Although the NMR method is non-destructive, all studies so far, with two exceptions, have been carried out on excised, perfused organs and tissues or have required some form of surgery for in situ measurements. The use of 'surface' radiofrequency coils does not require surgery, but is best suited for tissues close to the surface of the animals. We describe here 'topical magnetic resonance'--a new, non-surgical method for acquiring 31P-NMR spectra from a selected, localized place deep within an animal by modifying the main magnetic field, B0, using only static-field gradients. The method is conceptually similar to one spin-imaging method but primarily provides biochemical rather than spatial information. This new technique can be used in fundamental investigations into living systems, clinical diagnosis and the estimation of the efficacy of drug therapy.

Adenosine Triphosphate↗
PubMed1980

A study of changes in surface area and molecular interactions in phospholipid vesicles by condensed phase radioluminescence.

(1) The radioactive decay of tritium was used to excite 12-(9-anthroyloxy)-stearic acid. The resulting radioluminescence was observed by single-photon counting. A signal can only be observed if the emitting tritium is close enough to the absorbing fluorophore. This is accomplished by condensing the emitter and absorber into a lipid membrane. Therefore, we call the technique Condensed phase radioluminescence (CPR). (2) We present the theoretical background for the observed CPR signals. (3) We observed a large CPR signal when tritiated oleic acid was added to 12-(3-anthroyloxy)stearic acid micelles. (4) The phase transition of dimyristoyl phosphatidylcholine and dipalmitoyl phosphatidylcholine in unilamellar vesicles can be monitored with CPR, and the relative intensity change observed is directly related to the relative surface change at the centre of the bilayer. (5) Oleic acid and 12-(9-anthroyloxy)stearic acid exchange between dimyristoyl phosphatidylcholine and dipalmitoyl phosphatidylcholine vesicles. The labels show no real preference for the fluid phase of the dimyristoyl phosphatidylcholine vesicles. (6) CPR is a powerful method for studying distance and binding relationships in membranes.

Anthracenes↗
PubMed1980

N.m.r. studies of metabolism in perfused organs.

Several metabolites and intracellular pH in intact organs can be studied in a non-destructive manner by phorphorus nuclear magnetic resonance (31P n.m.r.). This possibility was demonstrated by us nearly five years ago. Since then we have developed the appropriate physiological techniques and improved the n.m.r. method for the study of animal hearts and kidneys. Here we described measurements aimed at clarifying three problesm. (1) Having measured the enzyme-catalysed fluxes between phosphocreatine and ATP by the method of saturation transfer n.m.r., we examine the relations between energy supply and heart rate in the isolated perfused rat heart. (2) We describe experiments to establish the validity of the perfusion model. For the first time, we report 31P n.m.r. measurements of an in vivo rat heart and compare the results with those obtained for the perfused rat heart. (3) Ischaemia and metabolism in rabbit kidneys is investigated to establish the relation between functional and metabolic recovery after a renal transplant operation.

Adenine Nucleotides↗
PubMed1980

Mapping of metabolites in whole animals by 31P NMR using surface coils.

The metabolic state of skeletal muscle and brain within intact rats is monitored using high resolution phosphorus nuclear magnetic resonance. Regional disturbances in metabolism (for example, localised ischaemia) are easily observed, indicating the diagnostic possibilities of the method. Measurements are made using 'surface' radiofrequency coils, which we discuss in detail.

Adenosine Triphosphate↗
PubMed1980

Analysis of rat heart in vivo by phosphorus nuclear magnetic resonance.

High-resolution 31P nuclear magnetic resonance spectra at 73.83 MHz are reported for rat heart in vivo. In live rats, it was possible to observe the cardiac content of ATP, phosphocreatine, and Pi. Only a small amount of whole-blood 2,3-diphosphoglycerate was observed in the spectra, precluding the possibility that blood phosphate compounds were masking the spectra of cardiac phosphate compounds. The 31P nuclear magnetic resonance spectra of in vivo and perfused rat hearts were similar and support the utilization of the perfused rat heart as a model system for studying high-energy phosphate metabolism of the heart in vivo. The dynamic flux of high-energy phosphate compounds was investigated by subjecting the rat to respiratory arrest. In this experiment, the heart followed the classic metabolic pattern known to occur during cardiac arrest; phosphocreatine and then ATP decreased in concentration while Pi increased in concentration. The 31P nuclear magnetic resonance analysis of rat heart in vivo is demonstrated to be a practical and feasible method for studying cardiac high-energy phosphate metabolism.

Adenosine Triphosphate↗
PubMed1979

Studies of acidosis in the ischaemic heart by phosphorus nuclear magnetic resonance.

1. Phosphorus-nuclear-magnetic-resonance measurements were made on perfused rat hearts at 37 degrees C. 2. With the improved sensitivity obtained by using a wide-bore 4.3 T superconducting magnet, spectra could be recorded in 1 min. 3. The concentrations of ATP, phosphocreatine and Pi and, from the position of the Pi resonance, the intracellular pH (pHi) were measured under a variety of conditions. 4. In a normal perfused heart pHi = 7.05 +/- 0.02 (mean +/- S.E.M. for seven hearts). 5. During global ischaemia pHi drops to 6.2 +/- 0.06 (mean +/- S.E.M.) in 13 min in a pseudoexponential decay with a rate constant of 0.25 min-1. 6. The relation between glycogen content and acidosis in ischaemia is studied in glycogen-depleted hearts. 7. Perfusion of hearts with a buffer containing 100 mM-Hepes before ischaemia gives a significant protective effect on the ischaemic myocardium. Intracellular pH and ATP and phosphocreatine concentrations decline more slowly under these conditions and metabolic recovery is observed on reperfusion after 30min of ischaemia at 37 degrees C. 8. The relation between acidosis and the export of protons is discussed and the significance of glycogenolysis in ischaemic acid production is evaluated.

Acidosis↗
PubMed1979

The ATPase inhibitor protein in oxidative phosphorylation. The rate-limiting factor to phosphorylation in submitochondrial particles.

1. Purified luciferase and luciferin were used to study the time course of phosphorylation in submitochondrial particles. The light emitted was detected by a single-photon counter, using a multichannel analyser, and the results were analysed by an 'on-line' digital computer. 2. Using NADH as substrate, phosphorylation showed, in general, four phases. These were (i) a period of increasing rate ('lag'); (ii) a period of constant (positive) rate; (iii) a period of zero net rate (plateau), when the phosphorylation potential was maintained at its equilibrium value, and (iv) a period of negative rate (atp hydrolysis) after all the oxygen has been consumed. 3. The lag phase, several seconds in length, was a function of the inhibitor protein content of the particles. It was decreased in particles treated to remove the inhibitor protein, either by prior energisation of the particles with NADH, or by addition of aurovertin, which competes with the inhibitor protein for the ATPase. It was concluded that the ATPase inhibitor inhibits both ATP synthesis and hydrolysis by the ATPase. 4. The rate constant for the release of the inhibitor protein from the energised membrane was determined from the time course of ATP production during the lag phase. The activation energy of this process was measured from the temperature dependence of the lag, and was shown to be 13.3 kcal/mol, lower than the activation energy of ATP synthesis or NADH oxidation. 5. The rate constant for inhibitor release was dependent on 'energisation' of the membrane, being lower in the presence of uncouplers. However, it was possible to decrease the rate constant considerably with agents that collapsed the membrane potential without uncoupling the membrane. It was concluded that the inhibitor protein responded to the membrane potential component of the energisation. 6. A kinetic model for energy-dependent dissociation of the ATPase-inhibitor complex is proposed.

Adenosine Triphosphatases↗
PubMed1979

A potassium ion diffusion potential causes adrenaline uptake in chromaffin-granule 'ghosts'.

Membrane vesicles ('ghosts') formed from bovine chromaffin granules accumulate adrenaline in response to a diffusion potential produced by adding K+ in the presence of valinomycin. This uptake occurs as a short (2--5 min) burst because of the transient nature of the diffusion potential. The potential-driven uptake is optimal at pH approximately 7.2, is inhibited by reserpine, and has an initial rate comparable with that of ATP-driven uptake. These results show that ATP-dependent adrenaline uptake may occur at least partly in response to the membrane potential generated by an electrogenic proton-translocating adenosine triphosphatase found in chromaffin-granule membranes.

Animals↗
PubMed1979

Non-destructive measurement of metabolites and tissue pH in the kidney by 31P nuclear magnetic resonance.

Phosphorus nuclear magnetic resonance (31P NMR) can be used as a non-destructive method for the simultaneous observation of the major phosphate-containing metabolites (ATP, ADP, nucleotide monophosphate, Pi, sugar phosphate) and intracellular pH in isolated rat kidney. The time course of changes in these metabolites and in cellular pH in the ischaemic kidney are examined at two temperatures and in the presence of different flushing media. ATP is rapidly depleted while the pH change is slower and shows biphasic behaviour. Pi production and total nucleotide (ATP and ADP) depletion also occur on the same time-scale as the tissue acidification. The relation of these observations to tissue viability is discussed and the possibility of extending the measurements to human organs is considered.

Adenosine Diphosphate↗