Inhibition of ischemia-induced dopamine release by omega-conotoxin, a calcium channel blocker, in the striatum of spontaneously hypertensive rats: in vivo brain dialysis study.
The effect of omega-conotoxin GVIA (CgTX), an N-and L-type voltage-sensitive calcium channel (VSCC) blocker, on the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum before and during transient cerebral ischemia in spontaneously hypertensive rats was studied using an in vivo brain dialysis technique. Continuous perfusion of CgTX in the striatum was started 20 min before ischemia and concentrations of dopamine and DOPAC in the dialysate were measured using HPLC with an electro-chemical detector. Before ischemia, both 10 and 100 microM CgTX significantly lowered the concentration of dopamine, to 49% of the basal values. DOPAC concentrations also decreased significantly, by 28 and 17%, respectively. Forebrain ischemia, produced by bilateral carotid artery occlusion, reduced striatal blood flow to less than 6% of the resting value in each group. During 20 min of ischemia, the vehicle group showed a marked increase in dopamine (175 times the basal concentration). In the 10 or 100 microM CgTX perfusion group, in contrast, dopamine release was significantly attenuated, to 38 or 29% of the vehicle group, respectively. DOPAC concentrations decreased during ischemia to 58% of the basal value in the vehicle group and 49% in both CgTX groups. These results indicate that the massive release of striatal dopamine during ischemia depends largely on the influx of extracellular calcium via CgTX-sensitive VSCCs.
Ooboshi
H
H
Second Department of Internal Medicine, Faculty of Medicine, Fukuoka, Japan.
Sadoshima
S
S
Yao
H
H
Nakahara
T
T
Uchimura
H
H
Fujishima
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D018492:Dopamine Antagonists; D010456:Peptides, Cyclic; D015102:3,4-Dihydroxyphenylacetic Acid; D020866:omega-Conotoxin GVIA; D004298:Dopamine