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Biomedical subjects

G Gerber

Publications and source records attributed to G Gerber.

At least 73 records · Page 4Linked to original sources
PubMed1990

Nucleotide and glutathione status in erythrocytes of children undergoing chronic hemodialysis under erythropoietin treatment.

Recombinant human erythropoietin (rhEPO) used for the treatment of children with renal anemia is an effective stimulus of erythroid proliferation and differentiation. The increases of reticulocytes and of the hematocrit values give the possibility to renounce further blood transfusions in dialysis patients. There are no beneficial in vivo effects of rhEPO on the glutathione status and on the nucleotide contents of red blood cells. Therefore, indices for stabilizing effects of rhEPO on the circulating red blood cells cannot be due to glutathione and nucleotide metabolism.

Adolescent↗
PubMed1990

Metabolism of purine and pyrimidine compounds in erythrocytes of tumor-bearing mice.

The pattern of purine and pyrimidine derivatives was studied in the erythrocytes of C3HA and ICR mice during Hepatoma 22 and Ehrlich ascites tumor cell growth. Concentrations of purine nucleotides, nucleosides and nucleobases of host erythrocytes were changed after the implantation of the tumors. The host erythrocytes markedly concentrated adenine and guanine nucleotides both during logarithmic and plateau phase of tumor growth (5th and 11-12th days after inoculation of the tumor). The contents of nucleosides and nucleobases in the red blood cells were decreased during the logarithmic growth phase but restored within the plateau phase.

Animals↗
PubMed1990

Effects of phenylhydrazine hydrochloride on energy metabolism in rabbit erythrocytes and reticulocytes.

The effects of 1, 5 and 20 mmol/l phenylhydrazine hydrochloride on energy metabolism of rabbit erythrocyte and reticulocyte were studied. Significant depression of glycolysis, accompanied by loss of adenine nucleotides, mainly due to an extensive decline of ATP, was found in erythrocytes. Energy metabolism of reticulocytes appears to be more sensitive to deleterious effects of this drug. The declines of ATP and sum of all adenine nucleotides, as well as the accumulation of hypoxanthine were twofold in reticulocyte-rich red cell suspensions compared with suspensions of mature erythrocytes. It can be concluded that these changes are the consequence of lower energy production due to phenylhydrazine hydrochloride-induced inhibition of oxidative phosphorylation.

Adenine Nucleotides↗
PubMed1989

Excitatory amino acid-mediated components of synaptically evoked input from dorsal roots to deep dorsal horn neurons in the rat spinal cord slice.

The participation of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the responses of deep dorsal horn neurons to single shock stimulation of dorsal roots was investigated using current- and voltage-clamp techniques. In the presence of Mg2+, superfusion of rat spinal slices with 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX), a potent antagonist of non-NMDA receptors, reversibly blocks fast excitatory synaptic responses elicited by low-frequency stimulation of dorsal roots and to a greater extent the responses to quisqualate than to kainate or NMDA. The synaptic response elicited in a zero-Mg2+ medium is less sensitive to CNQX. The CNQX-resistant component is however abolished by D-APV, a selective antagonist of NMDA receptor. Under voltage-clamp, the excitatory postsynaptic currents also showed an initial fast (CNQX-sensitive) and a late slow (2-amino-5-phosphonovalerate (APV)-sensitive, Mg2+-sensitive) component, both of which had similar thresholds but differed in their latency, time-to-peak and duration. These results support the concept that both non-NMDA and NMDA receptor channels are present in a majority of deep dorsal horn neurons and could be simultaneously activated by transmitter released from stimulated primary afferents.

2-Amino-5-phosphonovalerate↗
PubMed1989

Participation of excitatory amino acid receptors in the slow excitatory synaptic transmission in the rat spinal dorsal horn in vitro.

The participation of excitatory amino acid (EAA) receptors in the responses of deep dorsal horn neurons to repetitive stimulation of dorsal roots was investigated using a spinal slice preparation and current-clamp and voltage-clamp techniques. Using EAA receptor and substance P (SP) receptor antagonists and current-clamp, slow excitatory synaptic response evoked by 10-20 Hz stimulation consisted of two depolarizing components: an initial component lasting 1-5 s and a late-one of 1-3 min duration. The initial and late components of the slow excitatory postsynaptic currents (EPSCs) can also be distinguished on the basis of their voltage-dependence and sensitivity to Mg2+ ions, D-2-amino-5-phosphonovalerate (D-APV) and 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX). In the presence of Mg2+, the initial component of the slow EPSC increased with membrane hyperpolarization, whereas the late component decreased. In a zero-Mg2+ medium, the initial component was potentiated, but the late component was reduced, or unchanged. CNQX reduced the initial component. In a zero-Mg2+ solution, or at membrane potentials positive to -55 mV in 1 mM Mg2+, D-APV reduced or even abolished the initial component, whereas the late component was not modified by D-APV. We propose that slow excitatory synaptic response evoked in deep dorsal horn neurons by repetitive stimulation of primary afferents has two components, an initial transient component that requires activation of N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and a late longer-lasting peptidergic component that has been already described (Brain Res., 290 (1984) 336-341.

2-Amino-5-phosphonovalerate↗
PubMed1989

Interrelationships between purine nucleotide degradation and radical formation during intestinal ischaemia and reperfusion: an application of ion-pair high-performance liquid chromatography of nucleotides, nucleosides and nucleobases.

There are peroxidative changes during the reperfusion of the rat small intestine following a 1h period of total ischaemia. That is demonstrated by the increases of the concentrations of glutathione disulphide and of thiobarbituric acid-reactive substances. An important source of the active oxygen species leading to peroxidations is the degradation of purine nucleotides. The nucleotides and their derivatives were measured by an ion-pair reversed-phase high-performance liquid chromatographic separation in a single analysis within 40 min. Modification of the elution gradient resulted in a high resolution of nucleosides and nucleobases, including allopurinol and oxypurinol. The decrease of the nucleoside triphosphate concentration and the increase of nucleoside monophosphate concentration, followed by accumulations of nucleosides and nucleobases in the course of the ischaemia were measured. During reperfusion the nucleotide pools are filled up. Restoration of adenosine triphosphate and guanosine triphosphate can be accelerated by application of the xanthine oxidoreductase inhibitor allopurinol. Pretreatment of the animals with allopurinol also diminished the formation of glutathione disulphide and thiobarbituric acid-reactive substances.

Animals↗
PubMed1989

Mitochondrial metabolism of guanine nucleotides. Possible role of guanosine.

The catabolism of intramitochondrial guanine nucleotides was examined. During 30 min incubation of rat liver mitochondria at 37 degrees C in the presence of oligomycin and carboxyatractyloside, guanine and xanthine were formed and appeared in the medium. Under these conditions, the direct conversion of GMP to guanine by hypoxanthine-guanine phosphoribosyltransferase is suggested to be the main catabolic route within the organelles. Only very small amounts of guanosine were produced and detected both inside and outside the organelles. [14C]Guanosine and [14C]inosine were taken up by the mitochondria. Therefore, guanosine is suggested to be a precursor of intramitochondrial guanine nucleotides.

Animals↗
PubMed1989

Regulation of purine nucleotide metabolism in hypoxic liver and intestine of rats: radical scavenging effects of allopurinol and oxypurinol.

The relationship between nucleotide catabolism and generation of activated oxygen species was investigated in liver, hepatocytes and small intestine of rats. In severe hypoxia nucleotide degradation via xanthine oxidase and urate oxidase requires about half of the oxygen consumed. Data on the changes of nucleobase compounds in rat hepatocytes and small intestine during ischemia and reoxygenation and the effects of allopurinol and oxypurinol thereon are presented. From EPR measurements it is concluded that OH. radicals induce reactions of allopurinol yielding long-living products which are able to react with DMPO-OH with loss of its radical properties.

Allopurinol↗
PubMed1989

Radical formation in the rat small intestine during and following ischemia.

Oxidative loading during the reperfusion of the proximal jejunum of rats following a one hour-period of complete ischemia was demonstrated in in vivo-experiments by the increases of the GSSG: total glutathione ratio and the concentration of TBA-RS. The pretreatment of the animals with the xanthine oxidoreductase inhibitor allopurinol diminished the accumulation of GSSG and of TBA-RS. It was concluded that the purine nucleotide degradation is an important source of oxygen reduction products in reoxygenated small intestine. The tissue concentrations of nucleotides, nucleosides and nucleobases were measured by an ion-pair reversed-phase HPLC separation. There occurred fast declines of ATP and GTP concentrations during ischaemia leading to temporary increases of nucleoside mono- and diphosphate pools. The hypoxanthine concentration is increased about twentyfold during oxygen deficiency. The ATP and GTP restoration during the reperfusion was accelerated in presence of allopurinol. The shares of the beneficial allopurinol effects are not yet clarified.

Animals↗
PubMed1989

Identification and characteristics of a novel mitochondrial 5'-nucleotidase in rat liver.

In rat liver mitochondria there exists an AMP-dephosphorylating activity which converts external 5'-AMP to adenosine. It exhibits a pH optimum of 7.5 and a Km(AMP) of 0.085 mM. Furthermore, this activity is stimulated by magnesium (Km = 0.5 mM) and seems to be not affected by low concentrations of ATP or ADP. From the characteristics of the enzyme the existence of a 5'-nucleotidase in rat liver mitochondria which is localized on the outer surface of the inner mitochondrial membrane was concluded. The enzyme may be important for the production of cellular adenosine.

5'-Nucleotidase↗
PubMed1989

Multiple effects of phorbol esters in the rat spinal dorsal horn.

Spinal cord slice preparation and intracellular recording techniques were used to examine the effects of phorbol esters on the sodium- and calcium-dependent action potentials, the excitatory synaptic transmission, the basal (resting) and the dorsal root stimulation-evoked release of 9 endogenous amino acids, including glutamate and aspartate, and the responsiveness of the rat dorsal horn neurons to excitatory amino acids (glutamic, kainic, quisqualic, and N-methyl-D-aspartic). 4-beta-Phorbol-12, 13-dibutyrate and 4-beta-phorbol-12, 13-diacetate produced minor alterations in membrane potential and resistance, but they broadened the sodium-dependent action potential and reduced the duration of the calcium-dependent action potential. In addition, phorbol esters caused a marked and long-lasting increase in the amplitude and the duration of excitatory postsynaptic potentials (EPSPs) evoked in dorsal horn neurons by orthodromic stimulation of a lumbar dorsal root. Phorbol esters produced a brief increase in the basal and electrically evoked release of endogenous excitatory (glutamic, aspartic) and inhibitory amino acids (glycine, GABA). In addition, the rates of release of alanine, serine, and threonine were also elevated. In the presence of TTX, phorbol esters selectively enhanced, in a reversible manner, the depolarizing responses of dorsal horn neurons to N-methyl-D-aspartic acid and L-glutamate but not the responses to kainic or quisqualic acids. The potentiation of the NMDA response was blocked by APV, a specific NMDA receptor antagonist. Thus, phorbol esters appear to enhance excitatory synaptic transmission in the rat spinal dorsal horn slice preparation by acting both at pre- and postsynaptic sites. Phorbol esters could potentiate excitatory synaptic transmission by acting predominantly at a postsynaptic site (NMDA receptor), since the duration of the increased responsiveness of dorsal horn neurons to glutamate and NMDA correlates better with the enhancement of EPSPs than with the increased release of the stimulation-evoked glutamate and aspartate. The increased release of endogenous amino acids is consistent with a presynaptic (terminal) site of action, but it could also be explained by enhanced interneuronal activity. Although our results suggest that in the rat spinal dorsal horn protein kinase C may have a role in controlling the release of putative excitatory and inhibitory neurotransmitters and may also be involved in the regulation of postsynaptic NMDA receptors, the identity of endogenous substance(s) participating in these effects is presently unknown.

Action Potentials↗
PubMed1989

Nucleotide degradation and radical formation in ischemic and reperfused small intestine.

Peroxidative loading during the reoxygenation of the rat small intestine following a complete ischemia was demonstrated in in vivo-experiments by the increases of the glutathione disulphide (GSSG): total glutathione ratio and the concentration of thiobarbituric acid-reactive substances (TBA-RS). The pretreatment of the rats with allopurinol diminished the accumulation of GSSG and of TBA-RS. From these effects was concluded that the purine nucleotide degradation is an important source of oxygen reduction products leading to peroxidations. The concentrations of nucleotides, nucleosides and nucleobases were measured by an ion-pair reversed-phase HPLC. The restoration of ATP and GTP concentrations during the reoxygenation period was accelerated by the application of allopurinol.

Adenine Nucleotides↗
PubMed1989

Nucleotide concentrations in hepatocytes during anoxia and reoxygenation in presence of allopurinol and oxypurinol.

In hepatocytes of starved rats nucleotide, nucleoside and nucleobase concentrations were measured during and following anoxia. A complete restoration of ATP is observed during reoxygenation after anoxic periods less than 60 minutes. GTP cannot be completely restored after 30 minutes of anoxia. Allopurinol and oxypurinol do not accelerate the ATP and GTP restoration. IMP, adenosine and AMP concentrations are increased in presence of allopurinol or oxypurinol during anoxia and reoxygenation.

Adenosine Triphosphate↗
PubMed1989

The adenine nucleotide catabolism in nonphosphorylating mitochondria of different tissues.

The degradation of endogenous adenine nucleotides was compared in mitochondria isolated from mouse and rat liver, rat renal cortex and solid hepatoma. Mitochondria were incubated for 30 min at 37 degrees C in the presence of carboxyatractyloside and oligomycin. In rat liver mitochondria ATP, ADP and AMP were degraded by about 25% each, whereas in kidney and hepatoma mitochondria a rapid decline of ATP and ADP but no change in the AMP contents were observed. Main products formed were adenosine, inosine and hypoxanthine in all mitochondria examined. Compartment studies revealed that the main route of intramitochondrial adenine nucleotide catabolism seems to proceed via AMP dephosphorylation and subsequent adenosine deamination.

Adenine Nucleotides↗
PubMed1989

A computer assisted method to control the steady state of an ATP-regenerating assay.

A mathematical procedure is presented which permits to calculate the steady-state concentrations of AMP, ADP and ATP in an ATP-regenerating assay containing pyruvate kinase and lactate dehydrogenase as auxiliary enzymes. The accuracy of this procedure is demonstrated by the agreement of the calculated concentrations with the experimental data obtained in measurements of mitochondrial ATPase activities. The computer-assisted procedure can be employed (a) to determine extremely low adenine nucleotide concentrations which are difficult to obtain by direct measurements and (b) to adjust and to optimize the assay conditions according to the specific requirements of the experiment, including high concentrations of ATP and prescribed ATP/ADP ratios.

Adenosine Diphosphate↗
PubMed1989

Purine compounds in mitochondria: a quantitative evaluation.

Applying a recently developed reverse-phase ion-pair HPLC technique we determined purine compounds in acid extracts of mitochondria isolated from rat and mouse liver, rat renal cortex, and hepatoma. Intramitochondrial purine nucleosides and bases were evaluated quantitatively for the first time. All mitochondria examined contain significant amounts of adenosine, guanosine, inosine, guanine, and hypoxanthine. Moreover, IMP was identified in all extracts. Adenine was detected in traces only. These results are in accordance with the concept of mitochondrial metabolism of purine compounds.

Animals↗
PubMed1989

Changes in the nucleotide metabolism of Ehrlich ascites tumour cells during their growth in vivo.

During the transition of Ehrlich mouse ascites tumour cells from the proliferating into the resting phase of growth a tremendous loss of purine and pyrimidine compounds was quantitated by ion-pair reversed-phase high performance liquid chromatography. This change is accompanied by a distinct decline in the incorporation rates of adenine, hypoxanthine, and adenosine. Inorganic phosphate stimulates the low rate of hypoxanthine incorporation of cells in the plateau phase, but lacks any effect on the high rate during proliferation. The mitochondria suffer structural deteriorations and decrease in their cellular content in the course of the plateau phase; however, other changes were not seen by morphometric analysis. The interrelations between nucleotide metabolism, mitochondrial content and the rates of formation and consumption of ATP are discussed.

Adenine↗