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Biomedical subjects

J H Quastel

Publications and source records attributed to J H Quastel.

At least 19 recordsLinked to original sources
PubMed1985

The development of biochemistry in the 20th century.

This lecture consists of a short appraisal of some of the main features that have characterized the growth of biochemistry during the course of the 20th century. It dwells on the early impacts of vitalism, the emergence and elucidation of the vitamins, the discovery of coenzymes, the concept of active centres of enzymes, the development of experimental techniques (including the use of isotopes), the genetic code, and on the development of molecular biology and closely allied fields of investigation. It concludes with a consideration of the influence of the study of membranes and of neurochemistry on current biochemical thought.

Animals↗
PubMed1977

Effects of N-methylamino acids and convulsants on spontaneous action potentials in guinea-pig cerebellar slices.

1. N-methyl-gamma-aminobutyrate (N-methylGABA), N-methylglycine, N-methyltaurine and N-methylbeta-alanine diminished the frequency of spontaneous spike discharges in guinea-pig cerebellar slices. Usually a weak excitatory effect preceded the inhibition. 2. The inhibitory effects of N-methylGABA and N-methylbeta-alanine were competitively antagonized by both picrotoxin and strychnine. 3. The inhibitory action of N-methyltaurine was competitively suppressed by strychnine and by low concentrations of picrotoxin. 4. The inhibitory action of N-methylglycine was suppressed by strychnine but not by picrotoxin. The suppression was competitive at low concentrations of strychnine. 5. N-methylDL-glutamate brought about a strong inhibition followed by a strong excitation of the neurones. The inhibitory effects were competitively suppressed by both picrotoxin and strychnine. Neither convulsant affected the excitation. 6. Whereas L- or D-glutamate caused only excitation in the majority of cells examined, a small proportion of the cells exhibited inhibition preceding the excitation by L- or D-glutamate. Such inhibitory effects were suppressed by picrotoxin but not by strychnine. 7. Kinetic analyses of the dose-response curves for the N-methylamino acid in the presence or absence of the convulsant indicated that the number of molecules of the amino acid combining with the receptor site to produce a response was 3 for N-methylGABA, 2 for N-methylglycine, 3 for N-methyltaurine, 3 for N-methylbeta-alanine. The corresponding value was 1 for N-methylDL-glutamate (inhibition). The number of molecules of convulsant combining with the receptor site was calculated to be 2 for picrotoxin with N-methylGABA, N-methylbeta-alanine and N-methylDL-glutamate and 1 for strychnine with all N-methylamino acids examined.

Action Potentials↗
PubMed1977

Effects of acetylcholine on potassium-induced changes of water and sodium uptakes in cerebral cortex slices from the rat.

The increases in uptakes of water and of sodium ions that occur in rat brain cortex slices when they are incubated in a physiological saline-glucose medium in presence of a high concentration of potassium ions (105 muequiv./ml) are abolished by acetylcholine in presence of eserine but not by choline. Acetylcholine is effective at 20 micron but its optimal effect occurs at about 0.7 micron. Its action is suppressed by atropine and not by d-tubocurarine. The potassium-induced change of permeability of brain cell membranes to sodium ions occurs at a site different from the tetrodotoxin-sensitive channel of sodium entry, because the suppressive effects of acetylcholine and tetrodotoxin are apparently independent of each other. The acetylcholine effect does not occur in the absence of calcium ions from the incubation medium. It is suggested that the increase of cell calcium ions, brought about by high concentrations of potassium ions in the incubation medium, induces an increase of glial permeability to sodium ions, with a resultant change in the sodium gradient, and that this increase is suppressed by acetylcholine.

Acetylcholine↗
PubMed1977

Effects of acetylcholine on potassium-induced changes of GABA and taurine uptakes and release in cerebral cortex slices from the rat.

Acetylcholine, in presence of eserine, has little or no effect on the potassium-ion-suppressed concentrative uptakes of GABA and taurine by rat brain cortex slices in contrast with its effect on those of L-glutamate, L-aspartate, and glycine. Potassium ions at a concentration of 30 muequiv./ml in the incubation medium has a marked suppressive effect on the uptakes of GABA and taurine when there is no apparent change in the sodium ion content of the brain tissue. It is concluded that some factor, besides the change in sodium gradient, operates in the mechanism of potassium suppression of GABA and taurine uptakes. Acetylcholine diminishes the potassium-evoked release of endogenous GABA and taurine from brain slices. Its action is Ca2+ dependent and is diminished by atropine. Acetylcholine does not affect the potassium-accelerated release of GABA from brain slices previously loaded with this amino acid. The differences in uptake and release phenomena exhibited by GABA and taurine from those of L-glutamine and L-aspartate may be due to differences between the mechanisms, as well as the sites, of cerebral uptake and release of these two groups of amino acids.

Acetylcholine↗
PubMed1976

Action of amino acids and convulsants on cerebellar spontaneous action potentials in vitro: effects of deprivation of C1-, K+ of Na+.

(1) The inhibition of spontaneous action potentials in guinea pig cerebellar cortex slices by GABA, glycine, taurine and beta-alanine is maintained when C1- in the superfusion medium is almost completely replaced by NO3- or I-('permeant' anion), but the inhibition decreases in magnitude with repeated application of the amino acid. Replacement of C1- by sulfate or isethionate ('impermeant' anion) causes a conversion of inhibition by these amino acids to excitation. The initial excitation which is sometimes seen with these inhibitory amino acids in high C1- media is abolished when C1- is replaced by either permeant or impermeant anions. (2) Reduction of K+ in the medium causes an increase of inhibition by the inhibitory amino acids in the presence of high C1- and reduction of excitation when C1- is replaced by impermeant anion. (3) Excitation by GABA in impermeant anion (low C1-) media is unaffected by reduction of Na+ in the media by 50% but excitations by glycine, taurine, beta-alanine and L-glutamate are greatly reduced. (4). Excitation by GABA in impermeant anion (low C1-) media is abolished by picrotoxin and bicuculline which both suppress inhibition by GABA in a high C1- medium. Strychnine suppresses the effects of glycine, taurine and beta-alanine in either a low or high C1- medium. Bicuculline blocks the inhibitory effect of these three amino acids in a high C1- medium but does not affect their excitatory effects in a low C1- medium. (5) These results are consistent with the hypothesis that the inhibitory amino acids, GABA, glycine, taurine and beta-alanine, cause inhibition via increase of C1- (and perhaps K+) permeability and that glycine, taurine and beta-alanine also interact with strychnine-sensitive receptors mediating (perhaps indirectly) increased permeability to Na+ and, therefore, excitation in low C1- media.

Action Potentials↗
PubMed1976

Effects of amino acids and convulsants on spontaneous action potentials in cerebellar cortex slices.

1 Picrotoxin selectively and reversibly suppressed the inhibitory action of gamma-aminobutyric acid (GABA), but not that of glycine, taurine or beta-alanine, on the frequency of spontaneous spike discharges in guinea-pig cerebellar slices. Strychnine reversibly suppressed the inhibitory action of glycine, taurine or beta-alanine but had no effect on that of GABA. 2 GABA, glycine, taurine and beta-alanine showed an early excitatory effect that was unaffected by picrotoxin or strychnine. 3 Studies of the dose-response relations indicated a competition between the amino acid and the convulsant at a common receptor site. 4 Kinetic analyses of the dose-response relations for the amino acids in the presence or absence of picrotoxin or strychnine indicated that the number of molecules of amino acid combining with the receptor site in order to produce a response (inhibition or excitation) was 3 for GABA, 2 for glycine, 3 for taurine and 4 for beta-alanine. There appeared to be no evidence that the response was due to the cooperativity between the amino acid receptor complexes. The number of molecules of convulsant that combined with the receptor site was 1 for either strychnine or picrotoxin. 5 Mixtures of glycine with taurine or beta-alanine, in contrast to those with GABA, appeared not to give additive inhibitory effects.

Action Potentials↗
PubMed1974

Biochemistry.

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Biochemistry↗
PubMed1973

Control of synthesis and release of radioactive acetylcholine in brain slices from the rat. Effects of neurotropic drugs.

1. Studies of the synthesis and release of radioactive acetylcholine in rat brain-cortex slices incubated in Locke-bicarbonate-[U-(14)C]glucose media, containing paraoxon as cholinesterase inhibitor, revealed the following phenomena: (a) dependence of K(+)-or protoveratrine-stimulated acetylcholine synthesis and release on the presence of Na(+) and Ca(2+) in the incubation medium, (b) enhanced release of radioactive acetylcholine by substances that promote depolarization at the nerve cell membrane (e.g. high K(+), ouabain, protoveratrine, sodium l-glutamate, high concentration of acetylcholine), (c) failure of acetylcholine synthesis to keep pace with acetylcholine release under certain conditions (e.g. the presence of ouabain or lack of Na(+)). 2. Stimulation by K(+) of radioactive acetylcholine synthesis was directly proportional to the external concentration of Na(+), but some synthesis and release of radioactive acetylcholine occurred in the absence of Na(+) as well as in the absence of Ca(2+). 3. The Na(+) dependence of K(+)-stimulated acetylcholine synthesis was partly due to suppression of choline transport, as addition of small concentrations of choline partly neutralized the effect of Na(+) lack, and partly due to the suppression of the activity of the Na(+) pump. 4. Protoveratrine caused a greatly increased release of radioactive acetylcholine without stimulating total radioactive acetylcholine synthesis. Protoveratrine was ineffective in the absence of Ca(2+) from the incubation medium. It completely blocked K(+) stimulation of acetylcholine synthesis and release. 5. Tetrodotoxin abolished the effects of protoveratrine on acetylcholine release. It had blocking effects (partial or complete) on the action of high K(+), sodium l-glutamate and lack of Ca(2+) on acetylcholine synthesis and release. 6. Unlabelled exogenous acetylcholine did not diminish the content of labelled tissue acetylcholine, derived from labelled glucose, suggesting that no exchange with vesicular acetylcholine took place. In the presence of 4mm-KCl it caused some increase in the release of labelled acetylcholine. 7. The barbiturates (Amytal, pentothal), whilst having no significant effects on labelled acetylcholine synthesis in unstimulated brain except at high concentration (1mm), diminished or abolished (at 0.25 or 0.5mm) the enhanced release of acetylcholine, due to high K(+) or lack of Ca(2+). The fall in tissue content of acetylcholine, due to lack of Ca(2+), was diminished or abolished by pentothal (0.25 or 0.5mm) or Amytal (0.25mm).

Acetylcholine↗
PubMed1972

Effects of tetrodotoxin and anaesthetics on brain metabolism and transport during anoxia.

1. Tetrodotoxin, at concentrations at which it abolishes generation of action potentials in the nervous system, enhances by about 300% the rate of anaerobic glycolysis of brain-cortex slices from adult rats, or from adult and infant guinea pigs. This occurs to a greater extent in Ca(2+)-deficient incubation media than in Ca(2+)-rich media. Tetrodotoxin has no accelerative effect on cerebral aerobic glycolysis. 2. Tetrodotoxin does not affect the rate of anaerobic glycolysis of 2-day-old rat brain-cortex slices, nor that of adult rat kidney medulla, nor that of an extract of an acetone-dried powder of brain. 3. Tetrodotoxin does not affect the rate of penetration of glucose into brain slices. 4. Its effect is not apparent if it is added 10min or later after the onset of anoxia. 5. Its effect diminishes as the concentration of K(+) in the incubation medium is increased while that of Na(+) is decreased. 6. Its salient effect, at the onset of anoxia, is to diminish influx of Na(+) into, and efflux of K(+) from, the brain slices. 7. Substances that promote cerebral influx of Na(+), e.g. protoveratrine, sodium l-glutamate, diminish the accelerative action of tetrodotoxin. 8. It is concluded that tetrodotoxin exerts its effect on anaerobic glycolysis by suppressing, at the onset of anoxia, the generation of action potentials and thereby the accompanying influx of Na(+) and efflux of K(+). It is suggested that glycolytic stimulation occurs because a rate-limiting step, e.g. operation of pyruvate kinase, is stimulated by K(+) and depressed by Na(+). 9. Local anaesthetics behave in a manner similar to that of tetrodotoxin in enhancing cerebral anaerobic glycolysis. 10. Sodium Amytal has a marked effect at relatively high concentration. 11. Tetrodotoxin diminishes efflux of amino acids, particularly glutamate and aspartate, at the onset of anoxia.

Action Potentials↗