Different effects of L-, N- and T-type calcium channel blockers on striatal dopamine release measured by microdialysis in freely moving rats.
Using a microdialysis method, we have investigated effects of the voltage-dependent calcium channel blockers, verapamil, nicardipine, omega-conotoxin and flunarizine on the dopamine release and metabolism in the striatum of freely moving rat. Perfusion of verapamil (1-300 microM) and nicardipine (1-100 microM), an L-type calcium channel blocker, into the striatum through the dialysis membrane showed a dose-dependent decrease of dopamine release in the dialysate and slight increase of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Treatment of omega-conotoxin (0.1, 1 microM), an N-type channel blocker, decreased about 50% basal dopamine release and slightly decreased DOPAC and HVA levels. Treatment with flunarizine (10 microM), an T-type channel blocker, did not affect the dopamine release and metabolism. From these data, it appears that treatments of the L- and N-type voltage-dependent calcium channel blockers in rat striatum suppress basal dopamine release, but T-type blocker does not suppress it, suggesting that L-, N- and T-type calcium channels regulate in vivo dopamine release in a different mechanism.
Kato
T
T
Laboratory of Molecular Recognition, Graduate School of Integrated Science, Yokohama City University, Japan.
Otsu
Y
Y
Furune
Y
Y
Yamamoto
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005444:Flunarizine / Q000494:pharmacology; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology; D009043:Motor Activity; D009529:Nicardipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D008978:Mollusk Venoms; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D014700:Verapamil; D009529:Nicardipine; D005444:Flunarizine; D004298:Dopamine