Control of glutamate release by calcium channels and κ ‐opioid receptors in rodent and primate striatum

The modulation of depolarization (4‐aminopyridine, 2 m M )‐evoked endogenous glutamate release by κ‐opioid receptor activation and blockade of voltage‐dependent Ca 2+ ‐channels has been investigated in synaptosomes prepared from rat and marmoset striatum. 4‐Aminopyridine (4‐AP)‐stimulated, Ca 2+ ‐dependent glutamate release was inhibited by enadoline, a selective κ‐opioid receptor agonist, in a concentration‐dependent and nor ‐binaltorphimine ( nor ‐BNI, selective κ‐opioid receptor antagonist)‐sensitive manner in rat (IC 50 =4.4±0.4 μ M ) and marmoset (IC 50 =2.9±0.7 μ M ) striatal synaptosomes. However, in the marmoset, there was a significant (∼23%) nor ‐BNI‐insensitive component. In rat striatal synaptosomes, the Ca 2+ ‐channel antagonists ω‐agatoxin‐IVA (P/Q‐type blocker), ω‐conotoxin‐MVIIC (N/P/Q‐type blocker) and ω‐conotoxin‐GVIA (N‐type blocker) reduced 4‐AP‐stimulated, Ca 2+ ‐dependent glutamate release in a concentration‐dependent manner with IC 50 values of 6.5±0.9 n M , 75.5±5.9 n M and 106.5±8.7 n M , respectively. In marmoset striatal synaptosomes, 4‐AP‐stimulated, Ca 2+ ‐dependent glutamate release was significantly inhibited by ω‐agatoxin‐IVA (30 n M , 57.6±2.3%, inhibition), ω‐conotoxin‐MVIIC (300 n M , 57.8±3.1%) and ω‐conotoxin‐GVIA (1 μ M , 56.7±2%). Studies utilizing combinations of Ca 2+ ‐channel antagonists suggests that in the rat striatum, two relatively distinct pools of glutamate, released by activation of either P or Q‐type Ca 2+ ‐channels, exist. In contrast, in the primate there is much overlap between the glutamate released by P and Q‐type Ca 2+ ‐channel activation. Studies using combinations of enadoline and the Ca 2+ ‐channel antagonists suggest that enadoline‐induced inhibition of glutamate release occurs primarily via reduction of Ca 2+ ‐influx through P‐type Ca 2+ ‐channels in the rat but via N‐type Ca 2+ ‐channels in the marmoset. In conclusion, the results presented suggest that there are species differences in the control of glutamate release by κ‐opioid receptors and Ca 2+ ‐channels.British Journal of Pharmacology (1999) 127 , 275–283; doi: 10.1038/sj.bjp.0702523