Synaptosomal Uptake and Release of Dopamine in Rat Striatum After Hypoxia

Abstract

Hypoxia induces alterations of central monoaminergic transmission and of behavior. We studied the effect of hypoxia on adult and newborn rats to obtain more information about long-lasting changes of dopamine (DA) transmission caused by neonatal hypoxia. One single exposure of adult rats to hypoxia leads to short-term alterations of DA uptake: decreased affinity of the uptake carrier to DA (Km, 269.5% versus control) and a sharp increase of Vmax up to 301.4% resulting in an increase of total uptake of DA into the striatum synaptosomes. The K+-evoked DA release decreased to 69.5%. After 1 week of recovery all parameters are normalized. Chronic postnatal hypoxia (postnatal day 2-11) caused long-lasting changes of DA release and uptake opposite to those observed in adult rats. Three months after hypoxia, the K+-stimulated DA release was enhanced (132% of control), and the uptake was reduced due to decreased affinity of the uptake carrier system for the substrate (Km, 187% of control value). In conclusion, the alterations observed after chronic postnatal hypoxia reflect special adaptive processes that are related to the high plasticity of the immature neonatal brain and contribute to an increased DA function in the nigrostriatal system.

Early postnatal hypoxia induces long-term changes in the dopaminergic system in rats

“…The reports from literature concerning the effects of hypoxia on DA uptake are contradictory: decreased (Pastuszko et al, 1982) and increased (Freemann and Gibson, 1986;Odarjuk etal., 1987) DA uptakes have been reported. The findings reported in Table 3 seem to be in contrast to previous data (Odarjuk et al, 1987) when an increased high-affinity uptake was found after a 12 hour hypoxia. At that time we determined the uptake kinetics by using only 4 DA concentrations between 0.021aM and 0.1 gM and a Michaelis Menten model.…”

Hypoxia induces different responses of striatal high- and low-affinity dopamine uptake sites

“…That the high-affinity uptake kinetics remained unchanged in our experiments is in contrast to previous findings of Odarjuk et al (1987). Employing the same type of hypoxia these authors described a threefold increased V,,,axl whereas we observed an insignificant elevation of about 30%.…”

“…So far, only the effects of hypoxia directed to the high-affinity uptake have been studied. The results of these investigations are conflicting with decreased (Pastuszko et al, 1982;Saijoh et al, 1985), increased (Freeman and Gibson, 1986;Odarjuk et al, 1987), andunchanged (Wustmann, 1984;Freeman and Gibson, 1986) uptake having been reported.…”

“…The tissue was homogenized by hand in 320 mM sucrose containing (mM): Na2HPO4 (2.0); KH2PO4 (0.7); MgCl2 (1.0); Na2EDTA (3.0) at pH 7.3 (Odarjuk et al, 1987). The homogenates were centrifuged at 1200g for 12 min and the supernatants (S, fractions) used for the uptake measurements.…”

“…Fifteen microliters of S, fraction were preincubated at 37°C in a final volume of 0.5 mL of incubation medium containing (mM): NaCI (130); KC1 (1.7); KH2PO4 (1.3); Na 2HPO 4 (10.4); MgSO4 (1.3); CaCl2 (1.3); glucose (11); sucrose (17.3); ascorbic acid (1.1); Na 2EDTA (0.2); pargyline (Sigma, St. Louis, MO) (0.13) at pH 7.35 (Odarjuk et al, 1987) for 5 min. Uptake was started by addition of [ 3H]dopamine (Amersham, UK) and terminated after 30 s by vacuum filtration of 0.4 mL samples on nitrocellulose filters (pore size 0.45 µm; Sartorious, Gottingen, Germany).…”