Ischemia-induced changes in extracellular levels of striatal cyclic AMP: role of dopamine neurotransmission.
Dopamine has been demonstrated to be involved in the development of ischemic neuronal damage in the striatum. This detrimental effect of dopamine may involve activation of second messenger systems, such as the cyclic AMP (cAMP) cascade, which may enhance the susceptibility of striatal neurons to ischemia. In the present study, we have evaluated the relationship between ischemia-induced changes in cAMP and dopamine neurotransmission. Microdialysis probes were implanted in both striata, and a D1 antagonist (SCH-23390, 100 microM) was administered through one probe and modified Ringer's solution through the other. After a stabilization period, rats (n = 6) were subjected to 20 min of ischemia by two-vessel occlusion plus hypotension. Extracellular samples were collected from both striata, before, during, and after ischemia, and analyzed for cAMP by radioimmunoassay. Ischemia induced a significant increase in extracellular cAMP (means +/- SE, fmol/microliter; baseline: 4.35 +/- 1.1, ischemia: 12.2 +/- 1.98), which was also observed at 4 h of recirculation (mean level of 8.45 +/- 1.14). Treatment with the D1 antagonist significantly inhibited the rise in extracellular cAMP during ischemia and recirculation. These results indicate that an ischemia-induced surge in dopamine and activation of D1 receptors are involved in the generation of cAMP during ischemia and recirculation. Because activation of the adenylate cyclase cascade may modulate the effects of glutamate, generation of cAMP through this pathway may play a role in facilitating the injurious effects of dopamine during ischemia.
Prado
R
R
Department of Neurology, University of Miami School of Medicine, Florida 33101.
Busto
R
R
Globus
M Y
MY
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology*; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D017447:Receptors, Dopamine D1; D000242:Cyclic AMP; D004298:Dopamine