Oxygen dependence of glucose and acetylcholine metabolism in slices and synaptosomes from rat brain.

Previous studies have shown that a reduction in the O2 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 O2 tensions ranging from 760 to less than 1 torr, 14CO2 production and [14C]ACh synthesis from [U-14C]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 14CO2 production and [14C]ACh synthesis at an O2 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 O2 tensions. In synaptosomes, 14CO2 production and [14C]ACh synthesis from [U-14C]glucose, the levels of lactate and ATP, and the ATP/ADP ratio were unaltered if a minimum O2 tension of 19 torr was maintained. Despite the difference in sensitivities to decreases in O2 levels, there is a curvilinear relationship between [U-14C]glucose decarboxylation and [14C]ACh synthesis at various O2 tensions for both tissue preparations with a high coefficient of determination (R2 = 0.970). The difference in the metabolic sensitivity of slices and synaptosomes to a reduced O2 level may be explained by the greater distance O2 must diffuse in slices. The results are discussed in comparison with hypoxia in vivo.