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At least 55 records · Page 3Linked to original sources
PubMed1976

Adenosine phosphyorylase activity as distinct from inosine-guanosine phosphorylase activity in Sarcoma 180 cells and rat liver.

Adenosine phosphorylase (EC 2.4.2.-) activity present in Sarcoma 180 cells grown in culture and in rat liver, is shown to be distinct from inosine-guanosine phosphorylase by several criteria: (a) treatment of Sarcoma 180 cell extract with p-chloromercuribenzoate inhibited the two activities to a different extent, (b) adenine selectively protected the adenosine phosphorylase activity of Sarcoma 180 and rat liver extract against heat inactivation, while hypoxanthine selectively protected inosine-guanosine phosphorylase activity, (c) at nearly saturating substrate concentrations and using Sarcoma 180 extract, the rates of ribosylation of a mixture of adenine + hypoxanthine or adenine + guanine, but not of hypoxanthine + guanine, were found to be almost equal to the sum of their individual rates as measured separately, (d) inosine selectively inhibited the ribosylation of hypoxanthine and guanine catalysed by Sarcoma 180 and rat liver extract while 2-chloroadenosine selectively inhibited the ribosylation of adenine and N6-furfuryladenine, (e) pH vs. activity curves were similar with hypoxanthine or guanine as the substrate but they were markedly different from the curve with adenine as the substrate. The potential role of adenosine phosphorylase activity in vivo is discussed.

Adenine↗
PubMedDate not supplied

Blood storage XXII. Improvement in red blood cell 2,3-DPG levels at six weeks by 20 mM PO4 in CPD-adenine-inosine.

Inorganic phosphate has been known to assist red blood cell maintenance of ATP and in the presence of inosine to assist in the maintenance of 2,3-DPG. High concentrations of phosphate, while helping ATP maintenance, were found to be deleterious to 2,3-DPG maintenance in CPD-adenine preservatives. However, in the presence of inosine, concentrations of phosphate as high as 10 mM were advantageous to 2,3-DPG maintenance. The present study extends the observations on ATP and 2,3-DPG maintenance in CPD-adenine-inosine preservatives from the previous 10 mM to 20 mM phosphate. A high phosphate (20 mM) effect has been seen as improved maintenance of 2,3-DPG levels during the fifth and sixth weeks of storage of whole blood at 4C. This supports the previously reported observation of improved maintenance of 2,3-DPG in a 10 mM phosphate preservative. This is ten times the 2 mM phosphate concentration in CPD-adenine. In the low phosphate preservative (2 mM), 2,3-DPG maintenance is less than that in all of the higher phosphate preservatives after the second week of storage. ATP concentrations in this experiment show good maintenance throughout six weeks of storage.

Adenine↗
PubMed1978

Inosine: clinical results of ischaemic renal surgery.

Ten patients requiring ischaemic renal surgery for calculus or tumour were operated on with the kidney protected by perfusion with a room temperature solution of inosine. The warm ischaemic times ranged from 35 to 75 min (mean 57.1 min). Post-operative recovery was uneventful in all patients. No adverse cardiodynamic effects due to inosine were noted. There was only moderate transient depression in renal function as assessed by gamma camera renography and serum creatinine estimations. Three of the 10 patients have now been followed for over a year. The results with inosine perfusion are comparable to those obtained with hypothermic protection.

Adult↗
PubMed1979

Inosine may be an endogenous ligand for benzodiazepine receptors on cultured spinal neurons.

Mouse spinal neurons grown in tissue culture were used to study the membrane effects of the benzodiazepine flurazepam and the naturally occurring purine nucleoside inosine, which competes for benzodiazepine receptor sites in the central nervous system. Application of inosine elicited two types of transmitter-like membrane effects: a rapidly desensitizing excitatory response and a nondesensitizing inhibitory response. Flurazepam produced a similar excitatory response which showed cross-desensitization with the purine excitation. Flurazepam also blocked the inhibitory inosine response. The results provide electrophysiological evidence that an endogenous purine can activate two different conductances on spinal neurons and that flurazepam can activate one of the conductances and antagonize the other.

Animals↗
PubMed1975

Prevention of chronic experimental heart insufficiency by inosine.

The administration of inosine dosed 25 mg/kg daily during 10 1/2 months prevented the development of excentric cardiac hypertrophy on the background of experimental aortic stenosis in rats, reduced the lowering of the working capacity of the animals, and partially inhibited the full development of functional and morphological myocardial changes, detected by electrocardiographic, vectorcardiographic, microscopic, and electronmicroscopic examinations. Differences were found in the relative weights of the heart, thymus, liver and other organs; these findings attested to an anabolic activity of inosine. The results obtained justify the application of inosine for the prevention of excentric hypertrophy and decompensation of the heart in cardiac failures varying in etiology; any efficient preventive measure is of importance, because the degree of excentric hypertrophy is a factor influencing the survival of the patients.

Adrenal Glands↗
PubMed1977

The heart production in energy-depleted human erythrocytes induced by glucose, inosine and adenine.

The heat production (HP) of glucose deprived human red blood cells was measured, using glucose, adenine and inosine as substrates. Inosine induced a significantly higher HP than glucose and adenine induced no significant HP. At low pH the HP of glucose decreased more than that of inosine, corresponding to an equally lowered lactate production. The results indicate that it should be possible to use the system developed to study the functional state both of the complete glycolytic system and the lower part of it in intact red blood cells during various clinical conditions.

Adenine↗
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

[The effect of inosine, inorganic phosphates and pyruvate on erythrocyte glycolysis metabolites under conditions of preservation].

Human erythrocytes were stored as resuspensions in solutions containing citrate (Z), inosine + citrate (I), inosine + phosphate (IP), and inosine + phosphate + pyruvate (IPP). The storage was made at + 4 degrees C for 6 weeks; the initial pH-value amounted to 7.4 at + 4 degrees C. The cellular concentrations of 2.3 DPG, ATP, G6P, FDP and DOAP + GAP were determined. The following results were obtained: 1. During the storage in stored Z-blood the 2.3 DPG concentration will fall below 10% of its initial value; it will remain nearly unchanged in stored I-blood and will increase to 170% in stored IP-blood, to 270% of its initial value in stored IPP-blood. 2. The ATP concentration of cells will fall to about 50% of its initial value at the beginning of the storage of all stored blood. After that it will only increase to about 80% of its initial value in stored IP- and IPP-blood. 3. During the storage the G6P concentration will increase to the highest degree in stored IPP-blood and if high pyruvate concentrations are not present, it will have a reciprocal behaviour towards the FDP and triosephosphate level. The results were discussed in view of the regulation of glycolysis under storage conditions.

Adenosine Triphosphate↗
PubMedDate not supplied

[Clearance and transformation of inosine in the body].

In 5 patients with myocardial infarction the ways of the inosine transformation and its clearance rate following injection of this drug in an amount of 200 to 400 mg were studied. After inosine introduction into the organism it is shown to immediately break down to hypoxanthine which makes determination of its half-time body retention period practically impossible. The half-time body retention period for hypoxanthine was about 3 min. The beneficial influence of inosine on the myocardium is apparently due to stimulation of some glycolysis reactions and pentosophosphate shunt at the expense of riboso-1-phosphate.

Aged↗
PubMedDate not supplied

[Inosine synthesis by Bacillus subtilis mutants and their development in synthetic media].

The inosine synthesis by Bacillus subtilis mutants selected by the Institute of Genetics 265 and 21 and their development on the mineral medium were studied. The mutants behaved differently towards the sources and concentrations of carbon, nitrogen, phosphorus and magnesium as well as towards additions of tyrosine, histidine, adenine and uracyl. Optimal concentrations of the components of the mineral medium for the inosine synthesis by the Bac. subtilis mutants were determined. Under favourable conditions the mutants synthesized 8 to 10 mg/ml inosine for 120 hours.

Amino Acids↗
PubMed1979

Inosine di- and triphosphate synthesis in erythrocytes and cell extracts.

The ability to synthesize inosinetriphosphate was demonstrated in blood cells as well as in a variety of tissue extracts in spite of the presence of ITP pyrophohydrolase. At the expense of having sub-optimal conditions, an assay system was selected that completely repressed the hydrolyzing enzyme, thus permitting the accumulation of ITP. In an attempt to define the biosynthetic pathway of ITP, and since guanylate kinase has been implicated in the formation of ITP, the rate of synthesis of ITP and GTP in cell extracts was compared. The comparison of the specific activities of the [14C]-labeled hypoxanthine and guanine moieties of the inosine and guanosine phosphates formed during incubation with [8-14C]-inosine and [8-14C]-guanosine respectively, revealed striking differences in the relative rates of isotope incorporation. Tentative mechanisms are proposed to explain these differences. The data obtained thus far does not discard the possibility that ITP may be formed by stepwise phosphorylation and (or) by direct pyrophosphorylation of IMP.

Blood Platelets↗
PubMed1978

Guanosine triphosphate catabolism in human and rabbit erythrocytes: role of reductive deamination of guanylate to inosinate.

The reductive deamination of guanylate to inosinate was demonstrable but occurred at low rates in human and rabbit erythrocytes incubated in vitro with or without glucose. However, the process was considerably accelerated in erythrocytes incubated with deoxyglucose. In human erythrocytes incubated with deoxyglucose, deamination was the major pathway of catabolism of guanylate; little or no guanylate was dephosphorylated. In rabbit erythrocytes, guanylate was both deaminated and dephosphorylated. Inosinate formed from guanylate was metabolized only by dephosphorylation in human erythrocytes, but in rabbit erythrocytes, it was also converted to xanthylate.

Animals↗
PubMed1976

The existance of a group translocation transport mechanism in animal cells: uptake of the ribose moiety of inosine.

After exposure to inosine, transport-competent plasma membrane vesicles isolated from SV-40-transformed Bal/c 3T3 cells accumulate intravesicular ribose 1-PO4 at a concentration 200-fold greater than the extravesicular concentration. An analysis of the purine nucleoside phosphorylase activity distribution in various subcellular fractions, relative to other enzyme activities, indicated the presence of plasma membrane-associated purine nucleoside phosphorylase activity. The plasma membrane vesicles appear relatively impermeable to hypoxanthine. However, hypoxanthine, which is a competitive inhibitor of the transport reaction, is the only compound tested capable of mediating efflux of already accumulated ribose 1-PO4. In addition, hypoxanthine does not result in the efflux of transported uridine which is accumulated in these membrane vesicles as uridine. Exogenous ribose 1-PO4 neither results in counterflow nor does it inhibit the original uptake reaction. The following transport reaction is proposed: uptake occurs by group translocation, mediated by membrane-localized purine nucleoside phosphorylase. The data are consistent with sites for inosine and hypoxanthine being on the outer membrane surface whereas the ribose 1-PO4 site is only on the inner surface.

Adenine↗
PubMed1977

Effects of inosine on purine synthesis in normal and HGPRT-deficient human fibroblasts.

1. Incubation of normal and HGPRT-deficient fibroblasts with inosine results in increased PP-ribose-P concentrations. 2. The increased PP-ribose-P concentrations are accompanied by decreased rates of purine synthesis de novo, more marked in normal cells 3. Increased purine nucleotide concentrations during incubation with inosine provide a likely explanation for the inhibition of purine synthesis in normal cells 4. The lack of accelerated purine synthesis in mutant cells under these conditions is not fully explained by consideration of PP-ribose-P and purine nucleotide concentations.

Cells, Cultured↗
PubMed1977

Release of adenosine, inosine and hypoxanthine from the isolated guinea pig heart during hypoxia, flow-autoregulation and reactive hyperemia.

In an attempt to test the hypothesis whether adenosine is involved in the regulation of coronary flow adenosine, inosine and hypoxanthine were measured in the effluent perfusate and in the tissue of isolated guinea pig hearts under various experimental conditions. In addition, the release of 14C-adenosine, 14C-inosine and 14C-hypoxanthine was determined after prelabeling cardiac adenine nucleotides with 14C-adenine. The decrease in coronary resistance induced by hypoxic perfusion (30% and 20% in the gas phase) and during autoregulation was associated with a considerable increase in the release of adenosine and hypoxanthine. Under both conditions the concentrations of adenosine in the effluent perfusate were clearly within the coronary vasodilating range of exogenously administered adenosine. The tissue content of adenosine also increased significantly when the perfusion pressure was reduced. The release of 14C-adenosine closely paralleled the changes in coronary resistance during hypoxic perfusion, autoregulation and during reactive hyperemia. The specific activity of adenosine in the effluent perfusate, however, decreased substantially upon reduction of the oxygen supply to the heart, indicating that the release of 14C-adenosine does not provide an absolute measure of total adenosine release by the heart. Our data indicate that the greater part of the adaptive changes of vascular resistance during hypoxia and autoregulation can be attributed to adenosine which is formed at an enhanced rate under these conditions. However, other factors might be involved as well.

Adenosine↗
PubMed1978

Vasoconstriction after adenosine and inosine in the rat isolated hindlimb abolished by blockade of tryptaminergic mechanisms.

The isolated right hindlimb of the rat was perfused at a fixed flow rate through the femoral artery with heparinized blood from the carotid artery of a donor. Single injections of adenosine (1--300 microgram) induced a biphasic response, a long-lasting vasoconstriction preceded by a transient vasodilatation. Inosine (1--300 microgram) produced only vasoconstriction. After repeated administration of 300 microgram of these substances, the vasoconstriction became less prominent, and finally reverted to vasodilatation. The vasoconstrictor response to these substances (300 microgram) was also diminished or reverted to vasodilatation after pretreatment with reserpine or methysergide. From these results, it is concluded that vasoconstriction after adenosine or inosine may be mediated by 5-hydroxytryptamine released from the peripheral stores and that the intrinsic direct action of these substances on the femoral vascular bed is vasodilator.

Adenosine↗
PubMed1976

2' Derivatives of guanosine and inosine cyclic 3',5'-phosphates. Synthesis, enzymic activity, and the effect of 8-substituents.

A series of representative derivatives of guanosine cyclic 3',5'-phosphate (cGMP) and inosine cyclic 3',5'-phosphate (cIMP) which contained modifications in either the 2' position or the 8 and 2' positions were synthesized. Three types of derivatives were investigated: (1) derivatives in which the 2' position has been altered to produce a 2'-deoxynucleoside cyclic 3',5'-phosphate or a 9-beta-D-arabinofuranosylpurine cyclic 3',5'-phosphate; (2) 2'-omicron-acyl derivatives; and (3) doubly modified derivatives containing a 2' modification [as in (1) and (2)] and an 8-substitution. 2'-Deoxyinosine cyclic 3',5'-phosphate and 9-beta-D-arabinofuranosylhypoxanthine cyclic 3',5'-phosphate were obtained by HNO2 deamination of 2'-deoxyadenosine cyclic 3',5'-phosphate and 9-beta-D-arabinofuranosyladenine cyclic 3',5'-phosphate (ara-cAMP), respectively. Treatment of 8-bromo-2'-omicron-(p-toluenesulfonyl) adenosine cyclic 3',5'-phosphate with NaSH yielded the intermediate 8,2'-anhydro-9-beta-D-arabinofuranosyl-8-mercaptoadenine cyclic 3',5-phosphate, which was converted directly to 2'-deoxyadenosine cyclic 3',5'-phosphate (dcAMP) by treatment with Raney nickel. 8-Bromo-2'-omicron-(p-toluenesulfonyl) guanosine cyclic 3',5'-phosphate was converted to 8,2'-anhydro-9-beta-D-arabinofuranosyl-8-mercaptoguanine cyclic 3',5'-phosphate, and the latter was desulfurized with Raney nickel to give 2-deoxyguanosine cyclic 3',5'-phosphate. Ara-cAMP, 9-beta-D-arabinofuranosylguanine cyclic 3',5'-phosphate, and 9-beta-D-arabinofuranosyl-8-mercaptoguanine cyclic 3',5'-phosphate have been previously reported (Mian et al. (1974), J. Med. Chem. 17, 259). 8-Bromo-2'-omicron-acetylinosine cyclic 3',5'-phosphate and 8-[(p-chlorophenyl)thio]-2'-omicron-acetylinosine cyclic 3',5'-phosphate were produced by acylation of 8-bromoinosine cyclic 3',5'-phosphate and 8-[(p-chlorophenyl)thio]inosine cyclic 3',5'-phosphate, respectively; while 8-bromo-2'-omicron-butyrylguanosine cyclic 3',5'-phosphate was synthesized by bromination of 2'-omicron-butyrylguanosine cyclic 3',5'-phosphate.

Animals↗
PubMed1977

A species difference in nucleoside phosphorylase activity and inosine-stimulated insulin secretion in isolated islets of Langerhans.

Inosine is a potent simulant of insulin release from rat but not from rabbit islets of Langerhans. Further investigation showed that nucleoside phosphorylase activity is exceptionally low in rabbit islets. The ability of inosine to promote insulin release seems to be related to islet nucleoside phosphorylase activity, which can display marked species differences.

Animals↗