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Oxygen Dependence of Glucose and Acetylcholine Metabolism in Slices and Synaptosomes from Rat Brain
Author(s) -
Ksiezak Hanna J.,
Gibson Gary E.
Publication year - 1981
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1981.tb00456.x
Subject(s) - acetylcholine , torr , chemistry , medicine , endocrinology , metabolism , synaptosome , oxygen , biophysics , biochemistry , biology , in vitro , physics , organic chemistry , thermodynamics
Previous studies have shown that a reduction in the O 2 tension of the blood from 120 torr to 57 torr (hypoxic hypoxia) decreases brain acetylcholine (ACh) synthesis. To determine if this decrease is due to a direct impairment of ACh metabolism or to an indirect effect mediated by other neurotransmitter systems, we studied ACh formation in rat brain slices and synaptosomes. At O 2 tensions ranging from 760 to less than 1 torr, 14 CO 2 production and [ 14 C]ACh synthesis from [U‐ 14 C]glucose, the levels of lactate and ATP, and the ATP/ADP ratio were determined. In slices, the first decreases were observed in the rate of 14 CO 2 production and [ 14 C]ACh synthesis at an O 2 tension of 152 torr. The ATP level started to decline at 53–38 torr, and a reduction in the ATP/ADP ratio was first found at and below 19 torr. Lactate formation was maximally stimulated at 38–19 torr. Synaptosomes responded differently than brain slices to reduced O 2 tensions. In synaptosomes, 14 CO 2 production and [ 14 C]ACh synthesis from [U‐ 14 C]glucose, the levels of lactate and ATP, and the ATP/ADP ratio were unaltered if a minimum O 2 tension of 19 torr was maintained. Despite the difference in sensitivities to decreases in O 2 levels, there is a curvilinear relationship between [U‐ 14 C]glucose decarboxylation and [ 14 C]ACh synthesis at various O 2 tensions for both tissue preparations with a high coefficient of determination ( R 2 = 0.970). The difference in the metabolic sensitivity of slices and synaptosomes to a reduced O 2 level may be explained by the greater distance O 2 must diffuse in slices. The results are discussed in comparison with hypoxia in vivo.