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Biomedical subjects

T W Stone

Publications and source records attributed to T W Stone.

At least 253 records · Page 14Linked to original sources
PubMed1980

Neuronal (Na+,K+)-ATPase and the release of purines from mouse and rat cerebral cortex.

Slices of mouse or rat cerebral cortex were incubated with [3H]adenine or [3H]adenosine, and [14C]GABA. Purines and GABA could subsequently be released by ouabain. The release of purines previously shown to occur on restoring elevated K+ levels to normal was not mimicked by noradrenaline at concentrations which activate (Na+,K+)-ATPase. Potassium-free solutions evoked no release of purine during the test period, but resulted in a large release when K+ was restored to normal. K+-free solutions evoked an immediate release of GABA. It is concluded that (Na+,K+)-ATPase is not involved in purine release.

Animals↗
PubMed1980

4-Aminopyridine blockade of neuronal depressant responses to adenosine triphosphate.

1 Adenosine, adenosine monophosphate and adenosine triphosphate (ATP) depressed the firing rate of neurones in the rat cerebral cortex when applied by microinontophoresis. 2 4-Aminopyridine, also applied iontophoretically blocked the depressant effects of the purines, without affecting responses to gamma-aminobutyric acid (GABA). This blockade was effected against purine depressions of both spontaneous and glutamate-evoked activity, suggesting that the interaction occurred postsynaptically.

4-Aminopyridine↗
PubMed1980

Adenosine inhibition of gamma-aminobutyric acid release from slices of rat cerebral cortex.

1 The effect of purine compounds on the potassium-evoked release of 14C-labelled gamma-aminobutyric acid (GABA) has been studied in 400 micrometers slices of rat cerebral cortex in vitro. 2 Adenosine and adenosine 5' monophosphate (AMP) inhibited the release of GABA at 10(-5) to 10(-3) M. Adenosine triphosphate (ATP) produced a significant inhibition of release only at 10(-3) M. 3 Theophylline 10(-4) or 10(-3) M reduced the inhibitory effect of adenosine, but did not change basal release of GABA. 4 Dipyridamole 10(-5) M itself reduced evoked GABA release, but did not prevent the inhibitory effect of adenosine, implying that adenosine was acting at an extracellularly directed receptor. 5 Calcium removal or antagonism by verapamil reduced the evoked release of GABA, but adenosine did not produce any further reduction of the calcium-independent release. This may indicate that the inhibitory effect of adenosine on GABA release results from interference with calcium influx or availability within the terminals.

Adenosine↗
PubMed1980

Blockade of striatal neurone responses to morphine by aminophylline: evidence for adenosine mediation of opiate action.

1 The responses of cortical and striatal neurones to morphine and adenosine applied iontophoretically have been studied in the male rat. 2 The majority of cells (57%) within the corpus striatum were profoundly inhibited, and a smaller proportion (18%) excited by morphine. Adenosine depressed the firing rate of 30/44 cells in the striatum, excitation never being observed. In contrast, the responses of cortical cells to morphine were typically weak and required longer ejection pulses to effect comparable changes in firing rate. 3 Aminophylline applied iontophoretically, as an anion, proved able to antagonize reversibly both morphine and adenosine in parallel. 4 On a number of cells, gamma-aminobutyric acid (GABA) was used as a control depressant but aminophylline did not appear to reduce these responses. 5 The responses to morphine (both inhibitory and excitatory) were not easily antagonized by naloxone. Typically, excitatory reponses were easier to antagonize than the inhibitory ones. 6 It is concluded that a consequence of the interaction of morphine with its receptors may be the release of adenosine which subsequently produces the inhibition observed with morphine.

Adenosine↗
PubMed1980

Characteristics of the release of adenosine from slices of rat cerebral cortex.

1. The characteristics of the release of adenosine have been examined from slices of rat cerebral cortex after incubation with [3H]adenine or [3H]adenosine. 2. Increasing the potassium concentration of the extracellular medium to 36 or 54 mM did not evoke any release, but release was observed in the first post-potassium sample. This occurred whether potassium was present for 2 or 10 min. 3. Calcium-free solutions or verapamil prevented the post-potassium release of tritium. Tetraethylammonium bromide and 4-aminopyridine had no effect. 4. Ouabain (100 microM) induced the release of tritium, and did not prevent an additional increment of release after potassium stimulation. Ouabain induced release did not occur in calcium-free or sodium-free media, but was increased in low calcium (0.1 mM) medium. 5. It is concluded that the characteristics of adenosine release are unlike those of conventional neurotransmitters. It is suggested that the release is associated with the influx of sodium and calcium ions through sodium channels.

Adenosine↗
PubMed1980

Aminophylline and theophylline derivatives as antagonists of neuronal depression by adenosine: a microiontophoretic study.

Aminophylline, theophylline, etamiphylline and diprophylline have been tested as antagonists of neuronal inhibition produced by microiontophoretically applied adenosine, when ejected as cations or anions. Aminophylline proved to be an effective adenosine antagonist when ejected as an anion, especially from alkaline solution. Anionic theophylline was also effective but less so, and on a smaller proportion of neurones. Ethylenediamine and hydroxyl ions had no effect on adenosine responses. GABA depressions were unaffected by any of the methylxanthines at the time of adenosine blockade. Cationic ejection from aminophylline or ethylenediamine barrels produced a depression of unit firing on about one third of the cells tested, but no antagonism of adenosine was observed. It is concluded that the anionic ejection of aminophylline from alkaline solution, or of etamiphylline of diprophylline, yields potentially useful antagonists of adenosine for iontophoretic experiments.

Adenosine↗
PubMed1979

Antidepressant drugs potentiate suppression by adenosine of neuronal firing in rat cerebral cortex.

Adenosine and AMP (5'-adenosine monophosphate) applied by microiontophoresis produced depression of neuronal firing rates in cerebral cortex. A number of antidepressant drugs including examples which are known not to affect noradrenaline uptake systems, potentiated the depressant purine effects. Noradrenaline responses were unaffected or reduced. Purines may therefore be important in the mechanism of action of antidepressant drugs.

Adenosine↗
PubMed1979

Amino acids as neurotransmitters of corticofugal neurones in the rat: a comparison of glutamate and aspartate.

1 The relative sensitivities to aspartate and glutamate of neurones receiving a corticofugal innervation were examined by microiontophoresis, and compared with the relative sensitivities of neurones not appearing to receive such an input.2 On all the cells tested, glutamate appeared to be a more potent excitant than aspartate in terms of neuronal response size or effective dose.3 DL-alpha-Aminoadipate (alphaAA) reduced the excitatory amino acid responses on all the neurones tested. On many of these cells a control excitation could be produced, by acetylcholine or hydrogen ions, which was in most cases unaffected by doses of alphaAA producing antagonism of amino acid excitation.4 On 70% of the cells, aminoadipate showed no selectivity for aspartate compared with glutamate but a differential action, involving blockade of aspartate but not glutamate, was apparent on the other 30%.5 Doses of alphaAA which selectively reduced responses to aspartate had no effect on short latency evoked spikes, but doses which also reduced responses to glutamate reduced the short-latency synaptic excitation induced by electrical stimulation of either the surface of the cerebral cortex, or of the pyramidal tracts in the medulla.6 These findings suggest that corticofugal neurones having an excitatory action on cells in various parts of the brain may use an amino acid, probably glutamate, as a common neurotransmitter.7 As no significant difference could be demonstrated in the potency ratios of glutamate:aspartate on monosynaptically activated cells compared with other cells, doubt is cast on the validity of drawing conclusions about transmitter identity from potency ratios alone, without the support of antagonist studies.

2-Aminoadipic Acid↗
PubMed1979

Selective antagonism by benzodiazepines of neuronal responses to excitatory amino acids in the cerebral cortex.

1 The recently discovered benzodiazepine receptor exists in high concentration in the cerebral cortex. We have, therefore, examined the effects of diazepam and chlordiazepoxide on cortical neurone responses to excitatory and inhibitory amino acids and acetylcholine, in the cortex of rats anaesthetized with urethane.2 Chlordiazepoxide applied by microiontophoresis reduced the responses to glutamate and aspartate but acetylcholine responses were unaffected on most cells even by much higher doses of benzodiazepine. gamma-Aminobutyric acid (GABA) and taurine responses were unaffected on most cells, but were reduced on 4 of 25 units. After intravenous diazepam, responses to GABA and taurine were reduced on 3 cells and unchanged on 11.3 On Purkinje cells in the cerebellum a number of cells (5 of 16) exhibited a substantial increase in responses to GABA and taurine following intravenous or iontophoretic application of benzodiazepines.4 It is suggested that the highly selective reduction of excitatory amino acid responses in the cerebral cortex may be of particular relevance to the behavioural effects of benzodiazepines.

Acetylcholine↗
PubMed1979

Glutamate as the neurotransmitter of cerebellar granule cells in the rat: electrophysiological evidence.

1 Glutamate and the excitatory aminoacid antagonist, alpha-aminoadipic acid (alphaAA), have been applied by microiontophoresis to Purkinje cells in the rat cerebellum. 2 Glutemate produced excitation of Purkinje cells and alpha AA selectively reduced that excitation without affecting responses to acetylcholine or hydrogen ions. 3 Monosynaptic spikes were evoked in Purkinje cells by stimulating the parallel fibres. alpha AA had little effect on these spikes when applied alone. 4 When the Purkinje cell excitability was reduced by the iontophoresis of gamma-aminobutyric acid, alpha AA then produced railure of the monosynaptic spike on 10 of 13 Purkinje cells, in doses shown to be selectively antagonistic towards aminoacids. 5 These results support neurochemical evidence that glutamic acid may be the neurotransmitter released by granule cell parallel fibres.

2-Aminoadipic Acid↗