High‐Affinity Uptake of Spermine by Slices of Rat Cerebral Cortex

Harman, R J; Shaw, Graham G.

doi:10.1111/j.1471-4159.1981.tb00409.x

Cited by 63 publications

(24 citation statements)

References 28 publications

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“…Since the uptake of 5.7 x 1O-9M tPH]-spermine is sodium-dependent. temperaturedependent and strongly susceptible to inhibition by metabolic inhibitors (Harman & Shaw, 1980b), properties which are consistent with neuronal transport, the release of spermine at this concentration in response to raised potassium concentrations may possibly reflect the depolarization of neuronal elements. Evidence is increasing that the potassiumevoked release of GABA from preparations which are rich in glia is independent of the presence of calcium ions (Sellstrom & Hamberger, 1977;Neal & Bowery, 1979) though Minchin & Iversen (1974) have reported calcium-dependent release from glia in rat dorsal root ganglia.…”

Section: Discussionmentioning

confidence: 96%

“…The potassium-induced release of spermine is only found to be calcium-dependent at an initial spermine uptake concentration of 5.7 x 10-9 M [:'H]-spermine. At this concentration, approximately 85% of the uptake occurs via a 'very high' affinity system (Km = 3.7 x 10-9 M) (Harman & Shaw, 1980b). On increasing the spermine uptake concentration, release is no longer calcium-dependent.…”

Section: Discussionmentioning

confidence: 99%

“…The present findings indicate that spermine release from rat cortex slices follows the classical pattern associated with the release of established neurotransmitters. There is also evidence that polyamines are active in influencing the firing rate of rat and cat brain stem neurones (Wedgwood & Wolstencroft, 1977) and the high affinity uptake system for spermine recently described (Harman & Shaw, 1980b) provides a means by which released spermine could be inactivated. R.J.H.…”

Section: Discussionmentioning

confidence: 99%

“…The method of uptake was essentially the same as that previously described (Harman & Shaw, 1980b). In brief, female Wistar rats (125 to 150g) were killed by decaptation and the brains rapidly removed.…”

Section: Methodsmentioning

confidence: 99%

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THE SPONTANEOUS AND EVOKED RELEASE OF SPERMINE FROM RAT BRAIN in vitro

Harman

Shaw

1981

British J Pharmacology

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The efflux of previously accumulated [3H]‐spermine from brain slices was measured using a continuous perfusion system. The spontaneous efflux was biphasic, consisting of an initial rapid efflux followed by a much slower release. The slices were depolarized by the addition to the medium of high potassium concentrations, ouabain or veratrine. At concentrations greater than 30 mM, potassium evoked a striking increase in the release of [3H]‐spermine. Following uptake in the presence of 5.7 × 10−9M[3H]‐spermine, K+‐evoked release was dependent on the presence of calcium ions. Release of spermine after uptake at 5.6 × 10−8m or 5.0 × 10−7m was not calcium‐dependent. The calcium‐dependent, K+‐stimulated release of spermine was inhibited in the presence of diphenylhydantoin (5 × 10−3m) or ruthenium red (10−3 m). Following uptake of 5.7 × 10−9m [3H]‐spermine in a sodium‐free medium, the calcium‐dependent, K+‐stimulated release was significantly inhibited. Ouabain (10−4m) caused a large but calcium‐independent increase in the efflux of [3H]‐spermine. Veratrine‐induced release was less substantial but was increased in a calcium‐free medium. Release evoked by veratrine was abolished in the absence of sodium. These results are discussed with respect to a possible ‘neurotransmitter’ or ‘neuromodulator’ role for spermine.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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THE SPONTANEOUS AND EVOKED RELEASE OF SPERMINE FROM RAT BRAIN in vitro

Harman

Shaw

1981

British J Pharmacology

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“…Previous work with ODC inhibitors has suggested that significant nolvamine accumulation can occur in the absence of ODC r 2 activity (23,25), and some estimates of polyamine reutilization rates indicate that as little as 30% of brain putrescine originates directly from the decarboxylation of ornithine (28). Because brain tissue, in particular, contains active uptake mechanisms for putrescine and the polyamines (29,30), acquisition of these compounds may be regulated separately from that of ODC during development. The question of whether similar mecha- Fig.…”

Section: Discussionmentioning

confidence: 99%

Biochemical Determinants of Growth Sparing during Neonatal Nutritional Deprivation or Enhancement: Ornithine Decarboxylase, Polyamines, and Macromolecules in Brain Regions and Heart

et al. 1987

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ABSTRACT. In order to elucidate the biochemical mechanisms operating to protect the brain from growth retardation in response to nutritional deprivation, comparisons were made of markers of cellular development in brain regions (cerebellum, cerebral cortex, midbrain + brainstem) and in a tissue which is not spared (heart). Nutritional status of neonatal rats was manipulated by increasing or decreasing the litter size beginning a t birth, and development of DNA, RNA, and proteins followed throughout the neonatal period. In addition, we assessed the activity and levels of ornithine decarboxylase and its metabolic products, the polyamines, which are known to coordinate macromolecule synthesis in immature tissue and to provide an early index of perturbed development. Cardiac ornithine decarboxylase and polyamines were altered within 48 h of initiating the changes in litter size, and the direction and magnitude of these biochemical effects were predictive of subsequent impairment or enhancement of organ growth and of cellular development. All three brain regions were buffered from growth alterations relative to the heart, but the cerebellum, which undergoes major phases of cell replication later than the other two regions, was somewhat less protected. The spared brain regions also showed evidence of compensatory hypertrophy in nutritional deprivation (increased protein/DNA ratio) which accounts for maintenance of growth in the presence of reduced cell numbers. Thus,-brain growth sparing involves specific cellular resDonses which are de~endent on the maturational profile of each brain region. -(~ediatu Res 22:599-604, 1987) Abbreviations ODC, ornithine decarboxylase ANOVA, analysis of varianceThe growth and development of the neonate are controlled, in large part, by nutritional status (1-3). Nevertheless, the developing nervous system is spared relative to the rest of the body, and although nutritionally induced reductions of brain size and cell number can be produced, these are generally of far smaller magnitude than those seen in nonneural tissues (1-3). Within the brain, a hierarchy of susceptibility to altered growth has been Received March 16. 1987 demonstrated, which depends primarily upon the maturational timetables for cellular replication and differentiation (1-3). The question remains. however, as to the mechanisms by which brain growth sparing occurs. Recent evidence has demonstrated that macromolecule synthesis during cellular replication is controlled through the ODC/polyamine pathway (4-6), and that early measurements of ODC activity and/or levels of the polyamines can predict subsequent toxicological or nutritional alterations of cellular maturation (6-1 1). In the current study, we have examined the biochemical basis of brain sparing through measurements of ODC, polyamines and macromolecules in brain regions and in a nonneuronal tissue whose growth is not spared (heart).The heart provides an excellent model for comparison with the brain because, like neuronal tissues, it ceases cellular replicatio...

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Glutamate Receptor Ion Channels: Activators and Inhibitors

Jane¹,

Tse²,

Skifter³

et al. 2000

Pharmacology of Ionic Channel Function: Activators and Inhibitors

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The classification of excitatory amino acid (EAA) receptors into N-methyl-oaspartic acid (NMDA) and non-NMDA receptors was based mainly on the discovery of selective agonists and antagonists (for a review see WATKINS and EVANS 1981). Thus the selective NMDA receptor antagonist, o-aaminoadipate blocked responses due to NMDA but not those due to quisqualate or kainate in the frog and rat spinal cord. Evidence for more than one type of non-NMDA receptor came from the observation that responses due to quisqualate but not those due to kainate are depressed by L-glutamic acid diethyl ester (GDEE) (McLENNAN and LOOGE 1979; while responses to kainate can be selectively antagonized by y"oglutamylglycine (rDGG) . In addition, receptors present on dorsal root fibers were shown to be sensitive to kainate but not quisqualate ). These observations resulted in the classification of EAA receptors into NMDA, quisqualate and kainate receptors. Such receptors are linked to ionic fluxes and are now known as ionotropic glutamate receptors (iGluRs) as distinct from the more recently discovered metabotropic glutamate receptors (mGluRs) linked to G-protein coupled metabolic changes (CONN and PIN 1997). The isoxazole analogue, (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) was reported to be more selective for the quisqualate type of iGluR than quisqualate itself (KROGSGAARO-LARSEN et al. 1980 and this led to this ionotropic receptor being renamed the AMPA receptor to avoid confusion with quisqualate-activated mGluRs (MONAGHAN et al. 1989;). Molecular biology has identified a large number of subtypes of both iGluRs and mGluRs.Progress in defining the role of EAA receptors in CNS function has also followed the development of receptor-selective antagonists. With the availability of NMDA receptor antagonists, it was possible to demonstrate a role of NMDA receptors in polysynaptic responses in the vertebrate spinal cord EVANS et al. 1979) and in hippocampal long term potentiation (COLLINGRIDGE et al. 1983;HARRIS et al. 1984

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High‐Affinity Uptake of Spermine by Slices of Rat Cerebral Cortex

Cited by 63 publications

References 28 publications

THE SPONTANEOUS AND EVOKED RELEASE OF SPERMINE FROM RAT BRAIN in vitro

THE SPONTANEOUS AND EVOKED RELEASE OF SPERMINE FROM RAT BRAIN in vitro

Biochemical Determinants of Growth Sparing during Neonatal Nutritional Deprivation or Enhancement: Ornithine Decarboxylase, Polyamines, and Macromolecules in Brain Regions and Heart

Glutamate Receptor Ion Channels: Activators and Inhibitors

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