The differential effect of ischemia on the active uptake of dopamine, gamma-aminobutyric acid, and glutamate by brain synaptosomes.
Ischemic stroke was induced in the Mongolian gerbil by left common carotid ligation. No change in uptake of [3H]dopamine, [3H]gamma-aminobutyric acid ([3H]GABA), or [14C]glutamate in synaptosomes obtained from the ischemic hemisphere was observed for up to 8 h. At 16 h after ligation, marked decrements in uptake were observed in animals showing hemiparesis: Uptake values expressed as a percent of the corresponding control hemisphere were 15.2% for dopamine, 28.9% for GABA, and 47.5% for glutamate. The differential sensitivity of dopamine terminals compared with glutamate terminals was highly significant. Separate experiments performed with synaptosomes isolated from the corpus striatum showed that the greater sensitivity to damage was intrinsic to the dopamine nerve terminal and not the result of regional variations in ischemic damage in brain. No bilateral effect of ischemia on dopamine uptake was evident. In animals exhibiting milder behavioral deficits (circling), a smaller and comparable decrement in uptake of dopamine, GABA, and glutamate was evident at 16 h, whereas animals not affected behaviorally showed no decrement at 16 h. Following uptake, the subsequent fractional release of neurotransmitter stimulated by 60 mM-potassium ions was not affected at any time point studied. Therefore, the loss in uptake at 16 h probably represents overt destruction of nerve terminals. Experiments with urethane used in place of pentobarbital for anesthesia during carotid occlusion showed that "protection" by pentobarbital was not a factor in the delayed response to ischemia. These results show that damage or destruction of nerve terminals is a delayed event following ischemia and that dopamine terminals are intrinsically more sensitive than glutamate terminals.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002339:Carotid Arteries / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005849:Gerbillinae; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D013574:Synaptosomes / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005971:Glutamates; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004298:Dopamine