Regulatory interactions among axon terminals affecting the release of different transmitters from rat striatal slices under hypoxic and hypoglycemic conditions.
An in vitro model of ischemia was utilized to study the effects of both oxygen and glucose depletion on transmitter release from rat striatal slices. The spontaneous and stimulation-evoked releases of tritiated dopamine, gamma-aminobutyric acid, glutamate, and acetylcholine were measured. Hypoxia increased the evoked release of glutamate and dopamine without effect on the resting release. In contrast, hypoglycemia itself increased the resting release of dopamine. Hypoxia in combination with hypoglycemia provoked a massive release of glutamate, dopamine, and gamma-aminobutyric acid. The effect on acetylcholine release was less pronounced. Ca2+ withdrawal partly reduced the effect of hypoxia combined with hypoglycemia on dopamine release and application of tetrodotoxin (1 microM) abolished it. MK-801 (3 microM), an N-methyl-D-aspartate receptor antagonist, attenuated the effect of hypoxia and hypoglycemia on [3H]dopamine release. omega-Conotoxin (0.1 microM) had a similar effect on stimulation-evoked release under a hypoxic condition. The D2 receptor antagonist sulpiride (100 microM) failed to enhance the release of [3H]acetylcholine in hypoxia combined with hypoglycemia. It was suggested that in response to hypoxia combined with hypoglycemia there is a massive release of glutamate due to the increased firing rate which in turn releases dopamine from the axon terminals through stimulation of presynaptic N-methyl-D-aspartate receptors. Dopaminergic inhibitory control on ACh release seems not to be operative under conditions of hypoxia combined with hypoglycemia.
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
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Milusheva
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Doda
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Pasztor
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Lajtha
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Sershen
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Vizi
D000818:Animals; D001369:Axons / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D018377:Neurotransmitter Agents