ACTIVATION OF HEXOSE MONOPHOSPHATE PATHWAY IN BRAIN BY ELECTRICAL STIMULATION IN VITRO

Abstract

Abstract— The incubation of cerebral cortical slices for 15 min in Krebs‐Ringer‐tris (pH 7.6) solution at 37°C with [1‐14C]glucose or [6‐14C]glucose as substrates yielded a C‐1:C‐6 14CO2 ratio of 1.21, whereas this ratio increased to 3.01 after the application of electrical stimulation (ES). Tissue levels of 6‐phosphoglu‐conate (6PG) and glucose 6‐phosphate (G6P), intermediary metabolites of hexose monophosphate (HMP) pathway, were 7 and 180 nmol/g tissue following 15 min incubation, and increased by 33 and 45 per cent respectively following the application of ES. Activities of 6‐phosphogluconate dehydrogenase (6PGDH, 6‐phospho‐d‐gluconate: NADP+ 2‐oxidoreductase, EC 1.1.1.44) and glucose‐6‐phosphate dehydrogenase (G6PDH, d‐glucose‐6‐phosphate: NADP+ 1‐oxidoreductase, EC 1.1.1.49), important enzymes in regulating the activity of HMP pathway, in cerebral cortical slices were 689 and 907 pmol/mg protein/min and were increased by 66 and 25 per cent respectively by the application of ES. Synaptosomal G6PDH and 6PGDH activities were maximally activated by the addition of 40 mm‐Na+ to the reaction mixture, whereas no activation by Na+ was observed in microsomal G6PDH and 6PGDH. Amobarbital inhibited more strongly the Embden–Meyerhof (EM) pathway than the HMP pathway, while imipramine had a stronger inhibitory effect on HMP pathway than on EM pathway in the electrically stimulated cerebral tissues. The present results indicate that the HMP shunt pathway in the cerebral cortex is activated by the application of ES in vitro, possibly at synaptic regions and may play an important metabolic and functional role in the brain.

The Rate of Utilization of Glucose Via Hexosemonophosphate Shunt in Brain

“…Evidently the net changes would depend on the slope of the regression line. This deduction is consistent with the experimental evidence showing that the concentration in brain of both glucose 6-phosphate and 6-phosphogluconate increased in rats under hypothermia and decreased under hyperthermia or after treatment with iodoacetate (Kauffman et al, 1969) and in brain slices after electrical stimulation (Kimura et al, 1974); however, Kauffman et al (1969) did not observe a marked increase in the concentration of 6-phosphogluconate with an increase in the concentration of glucose 6-phosphate in the brain of rats treated with phenobarbital or fluoroacetate. These considerations emphasize the involvement of the hexosemonophosphate shunt in the overall utilization of glucose in the adult brain.…”

“…granular layer of the cerebellum, transaldolase activity was three times that in other cell structures (Kauffman, 1972). The demonstration (a) of the operation of the hexosemonophosphate shunt (Appel and Parrot, 1970;Hothersall et al, 1981) and the presence of the enzymes and metabolites of the shunt pathway in isolated nerve terminals (Kaaman and Harkonen, 1977), (b) the enhancement of their activity by electrical stimulation in brain slices (Kimura et al, 1974) and crayfish stretch receptor neurons (Giacobini and Jongkind, 1968), after axotomy in superior cervical ganglion (Harkonen and Kauffman, 1974), and by neurotransmitters such as noradrenaline, 5-hydroxytryptamine, and acetylcholine in cerebral cortical fragments (Barondes et al, 1961) and synapses (Appel and Parrot, 1970), and (c) their inhibition by imipramine, an antidepressant (Kimura et al, 1974), provide compelling evidence of the involvement of the hexosemonophosphate shunt in synaptic events of neuronal activity.…”

The Functional Significance of the Pentose Phosphate Pathway in Synaptosomes: Protection Against Peroxidative Damage by Catecholamines and Oxidants

“…1. The increased PPP activity after electrical stimulation of the cerebral cortex (Kimura et al, 1974) can be related to the replenishment of neurotransmitter substances released by such stimulation (Alousi and Weiner, 1966). Such replacement is almost certainly not involved in the present experiments which relate solely to the effects of neurotransmitters added in vitro.…”

Aspects of Carbohydrate Metabolism in Developing Brain

“…Three lines of evidence add some weight to the suggestion of a linkage between the activity of the pentose phosphate pathway and neurotransmission. First is the observation that electrical stimulation of brain slices elevates the activity of the pentose phosphate pathway (O'Neill et al 1965, Kimura et al 1974. Secondly, a substantial portion of the total cellular activity of the pathway is localized in the large particle (synaptosomal) fraction (Bagdasarian and Hulanicka 1965, Baquer and McLean 1972); and thirdly, the activity of the pentose phosphate pathway in synaptomes can be strongly stimulated by the addition PPP + TCA cycle TCA cycle Glycolysis + of neurotransmitter substances such as noradrenaline and serotonin (Appel and Parrot 1970).…”