Search PubMed⌕ Search

Biomedical subjects

J R Griffiths

Publications and source records attributed to J R Griffiths.

At least 163 records · Page 9Linked to original sources
PubMed1979

Activation of AMP aminohydrolase during skeletal-muscle contraction.

AMP aminohydrolase activity is enhanced by 60% after 5 s tetanic stimulation of phosphorylase kinase-deficient mouse muscle and after 60 s tetanus in normal mice. During the recovery from tetanus the activity in the contralateral leg is similarly enhanced. The activation is stable to 1000-fold dilution and has a half-life of approx. 1 h.

AMP Deaminase↗
PubMed1977

Renal function after warm ischaemia. II. Marked protective effect of intravenous inosine given prior to 60, 90 and 120 min of warm ischaemia.

Rats were given 10 or 20 mg of inosine dissolved in 1 ml of 0.9% saline, or a control solution of 1 ml of 0.9% saline, intravenously 10 or 20 min before induction of left renal warm ischemia for 60 min. Further groups of rats were treated with 20 mg inosine or with saline alone 20 min before longer periods of warm ischeamia of 90 and 120 min duration. All animals had immediate contralateral nephrectomy. In all inosine-treated groups the mean plasma creatinine was lower than in their respective control groups and these differences were statistically highly significant.

Animals↗
PubMed1976

Conformational changes associated with transient activation of phosphorylase in glycogen particles. Studies using activity, electron-spin-resonance and phosphorus-nuclear-magnetic-resonance measurements.

1. Calcium-dependent transient phosphorylation of phorphorylase b has been monitored in a rabbit muscle glycogen particle fraction. Using a phosphorus nuclear magnetic resonance assay, the changes in concentrations of small phosphate-containing metabolites associated with this event have been measured. In addition, the conformation of phosphorylase has been monitored during transient activation by observing changes in the electron spin resonance signal from added spin-labelled phosphorylase. 2. The transient activation was associated with a loss of glucose-6-phosphate from phosphorylase b; newly formed phosphorylase a binds the nucleotides ADP, AMP, or IMP. Because of the fast interconversion of these nucleotides the species bound to phosphorylase a change throughout the process. 3. Lowering the [Mg2+] : [Ca2+] ratio during transient activation causes accumulation of ADP. Electron spin resonance data from spin-labelled phosphorylase shows that, under these conditions, ADP binding to phosphorylase a is potentiated. 4. Calcium-dependent activation in the glycogen particle fraction is compared to the activation of phosphorylase in vivo.

Animals↗
PubMed1976

Enhanced preservation of the ischaemic kidney with inosine.

The function of rat kidneys subjected to 60 minutes of warm ischaemia at body-temperature was notably protected by the prior administration of the purine nucleoside inosine as a 40 mg/ml solution maintained at 37 degrees C. With direct intrarenal arterial perfusion of the kidney at the onset of ischaemia or with intraperitoneal (i.p.) injection 40 minutes before ischaemia, the plasma-creatinine at 24 hours was significantly lower (P less than 0-001) than that of untreated 60-minute-ischaemia controls and not significantly different from that of non-ischaemic unilateral-nephrectomy controls. Intravenous inosine 20 minutes beforehand also afforded significant (P less than 0-01) protection. 7-day survival was 100% in 30 inosine-pretreated rats and 65% in 45 rats with all other types of pre-treatment (P less than 0-001). Although i.p. adenosine was better (P less than 0-05) than no treatment, i.p. inosine was better (P less than 0-02) than i.p. adenosine. Allopurinol, phenoxybenzamine, A.T.P., or cyclic A.M.P. caused no improvement over controls. Kidneys perfused with inosine maintained higher purine-nucleotide levels during ischaemia and rapidly resynthesised A.T.P. when blood-flow was restored in vivo.

Adenosine↗
PubMed1976

Conformational changes in glycogen phosphorylase studied with a spin-label probe.

Phosphorylase b and a were covalently modified on essentially one -- SH group per subunit by a spin label 4-(2-iodoacetamido)2,2,6,6-tetramethyl piperidinyloxyl. The labelled enzyme is fully active and exhibits all the characteristics of the native molecule. The electron spin resonance spectrum of the label depends on the nature of the ligand that is bound to the enzyme. This property of the spin label is used to study the interaction between the enzyme (both in the b and a forms) and activators (AMP, IMP, CMP), inhibitors (ADP, ATP, UDPG, glucose 6-phosphate), substrates (phosphate and glucose 1-phosphate) and other ligands (adenosine, beta-glycerol-2-phosphate). The interactions are analysed in terms of the apparent ligand dissociation constants and the multiplicity of conformations that this regulatory enzyme exhibits.

Adenosine Diphosphate↗
PubMed1976

Heterotropic interactions of ligands with phosphorylase b.

1. The interaction of rabbit muscle glycogen phosphorylase b with pairs of ligands has been examined. 2. The electron spin resonance spectrum of a spin label, covalently attached to the protein, provided information about dissociation constants, formation of ternary complexes and both negative and positive interactions between different ligand pairs. 3. AMP competes with a series of nucleotides (ADP, ATP, CMP aand cytosine) but with adenosine a ternary enzyme - AMP - adenosine complex can be formed. 4. ADP binding is tight and ADP inhibits the AMP activation of phosphorylase b in a physiologically important concentration range. 5. The substrates glucose 1-phosphate and glycogen tighten AMP binding in the ternary complex as does the competitive inhibitor UDPG. Inorganic phosphate is different in this respect. Gluconolactone, a transition state analogue, competes with glucose 1-phosphate (but not with glycogen) but does not prevent completely the binding of the sugar phosphate. 6. The effect of glucose b-phosphate on phosphorylase is rather complex as it 'formally competes' with both AMP and UDPG probably mediated by a conformational changes and not by 'direct' interactions with these two ligands. Glycerol 2-phosphate, a commonly used buffer for phosphorylase, also shows complex interactions.

Adenosine Monophosphate↗