Neurotransmitter Metabolism in Rat Brain Synaptosomes: Effect of Anoxia and pH

Pastuszko, Anna; Wilson, David F.; Erecińska, Maria

doi:10.1111/j.1471-4159.1982.tb06647.x

Cited by 95 publications

(45 citation statements)

References 28 publications

(34 reference statements)

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“…The former is consistent with the earlier postulate from this [15,16] and other [ 17,181 laboratories that the uptake of amino acid transmitters is fueled by a combination of the transmembrane electrical potential, i.e. [K']i/[K']e and the sodium concentration gradient.…”

Section: Discussionsupporting

confidence: 80%

Amino acid neurotransmitters in the CNS

Erecińska

Nelson

1987

FEBS Letters

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Carefully isolated, metabolically competent rat brain synaptosomes accumulate acidic amino acid neurotransmitters down to very low external levels. This supports the suggestion that nerve endings are involved in terminating transmission at the synapses and in maintaining Iow levels of these molecules in the external en~ro~ment in the brain. At saturating levefs of acidic amino acids, the rate of inward and outward movements of the Na+-amino acid compfex (exchange) is much faster than the net uptake. The transmembrane gradients of aspartate and glutamate approach each other under all conditions explored which indicates that these two amino acids share the same transport system.

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Section: Discussionsupporting

confidence: 80%

Amino acid neurotransmitters in the CNS

Erecińska

Nelson

1987

FEBS Letters

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“…In contrast, K+-evoked norepinephrine (NE) release is elevated in the cortical slices of Mongolian gerbils subjected to cerebral ischemia (3). On the other hand, depolarization-induced catecholamine release from the rat brain synaptosomes is unaffected by in vitro hypoxia (4).…”

mentioning

confidence: 87%

Mechanism of Pindolol-Induced Vasoconstriction in Isolated and Perfused Dog Coronary Arteries

Takata

Shimada

Kato

1993

Japanese Journal of Pharmacology

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ABSTRACT-By using rat brain cortical slices preloaded with [3H]norepinephrine, we examined whether ATP-sensitive K+ channels are involved in altered adrenergic neurotransmission during hypoxia. The tritium overflow evoked by transmural nerve stimulation (TNS) was significantly inhibited at 5 min of hypoxia and reached the maximum inhibition at 20 min. The inhibition of the TNS-evoked tritium overflow under a 20-min hypoxia was reversed by subsequent reoxygenation and was concentration-dependently antagonized by glibenclamide (0.1 and 1 pM). 86Rb+ efflux was increased after introduction of hypoxia and reached the peak value at about 20 min, which was concentration-dependently antagonized by glibenclamide (0.1-10 uM). Hypoxia decreased cortical ATP content. Linear correlations were mutually observed among the changes by hypoxia in the TNS-evoked tritium overflow, tissue ATP content and 86Rb+ efflux. The spontaneous tritium outflow was inhibited only after hypoxic periods of more than 16 min, the inhibition being reversed by reoxygenation and antagonized by 1 uM glibenclamide. These results suggest that the inhibition of rat central adrenergic neurotransmission during hypoxia may be associated with an activation of ATP-sensitive K+ channels. Keywords:Hypoxia, ATP-sensitive K+ channel, Central adrenergic neurotransmission, 86Rb+ efflux, ATP content Neuronal transmission in the brain is highly sensitive to the lack of oxygen (1). However, the effects of anoxia/ hypoxia or ischemia on adrenergic neurotransmission in the brain seem to be discrepant; the activity of nor adrenergic neurons is decreased in the rat cerebral cortex and hippocampus during in vivo hypoxia (2). In contrast, K+-evoked norepinephrine (NE) release is elevated in the cortical slices of Mongolian gerbils subjected to cerebral ischemia (3). On the other hand, depolarization-induced catecholamine release from the rat brain synaptosomes is unaffected by in vitro hypoxia (4).It is well accepted that oxygen deficiency or deprivation decreases the amount of high-energy phosphates (adeno sine 5'-triphosphate (ATP) and creatine phosphate) in the brain. A decreased ATP content is expected to open ATP-sensitive K+ (KATP) channels. Recent studies dem onstrated that KATP channels are present in the central nervous system (5) and modulate transmitter release in rat hippocampal CA3 neurons under anoxic conditions (6). On the other hand, antidiabetic sulfonylurea tol butamide, a KATP channel blocker, did not alter the anox ic response of rat hippocampal CAI neurons (7). Thus, it is likely that there are regional differences in the involve ment of KATP channels in the anoxic response. In addi tion, the localization of binding sites for sulfonylurea ([3H]glibenclamide) is heterogeneous in the rat brain and the motor neocortex is one of the five regions containing the highest concentrations of the sulfonylurea binding sites (8). We recently reported that KATP channels modu late electrically stimulated NE release from the rat motor neocortex slices under normoxic con...

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“…However, with complete ischemia, grey matter is more heavily involved. In grey matter neurotransmitter metabolism is extremely sensitive to even short periods of hypoxia [48]. Although the autoregulation adapts to long-standing hypertension [65], the small vessels gradually become affected struc-turally, with development of atherosclerosis and hyalinosis further reducing their autoregulatory capacity.…”

Section: Factors Regulating Cerebral Blood Jtowmentioning

confidence: 99%

Pathogenetic mechanisms in vascular dementia

et al. 1994

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Summary. Vascular dementia accounts for approximately20% of all cases of dementia and for about 50% in subjects over 80 years. Thromboembolism with multiple cerebral infarcts was considered to be almost the only pathogenetic pathway of vascular dementia, with multiinfarct dementia as its clinical manifestation. However, there is a great heterogeneity of vascular dementia syndromes and pathological subtypes, as documented by the number of pathogenetic mechanisms now known to underlie the clinical picture. They include thromboembolism and extracerebral and cerebral factors. Among the extracerebral factors are ischemic hypoxic dementia (i.e., dementia due to hypoperfusion), vasculitis, hyperviscosity and abnormalities of hemostasis. Among the cerebral factors are lipohyalinosis, cerebral amyloid angiopathy, disruption of the blood-brain barrier and altered regulation of cerebral blood flow. Therefore, the approach to vascular dementia should take the heterogeneity into account. In this context, the importance of non-infarct type should be considered; subcortical white matter disorder seems to be a noteworthy common pathway of vascular dementia produced by various vascular mechanisms. Finally, the heterogeneity of the vascular mechanisms involved in vascular d~mentia -namely hypoperfusion -might be a factor that can be positively influenced by targeted therapeutic intervention.

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Neurotransmitter Metabolism in Rat Brain Synaptosomes: Effect of Anoxia and pH

Cited by 95 publications

References 28 publications

Amino acid neurotransmitters in the CNS

Amino acid neurotransmitters in the CNS

Mechanism of Pindolol-Induced Vasoconstriction in Isolated and Perfused Dog Coronary Arteries

Pathogenetic mechanisms in vascular dementia

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