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

Abstract

1. The modulation of depolarization (4-aminopyridine, 2mM)-evoked endogenous glutamate release by a-opioid receptor activation and blockade of voltage-dependent Ca2+-channels has been investigated in synaptosomes prepared from rat and marmoset striatum. 2. 4-Aminopyridine (4-AP)-stimulated, Ca2+--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 (IC50 = 4.4 ± 0.4 μM) and marmoset (IC50 = 2.9 ± 0.7 μM) striatal synaptosomes. However, in the marmoset, there was a significant (~ 23%) nor-BNI-insensitive component. 3. In rat striatal synaptosomes, the Ca2+-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, Ca2+-dependent glutamate release in a concentration-dependent manner with IC50 values of 6.5 ± 0.9 nM, 75.5 ± 5.9 nM and 106.5 ± 8.7 nM, respectively. In marmoset striatal synaptosomes, 4-AP-stimulated, Ca2+-dependent glutamate release was significantly inhibited by ω-agatoxin-IVA (30 nM, 57.6 ± 2.3%, inhibition), ω-conotoxin-MVIIC (300 nM, 57.8 ± 3.1%) and ω-conotoxin-GVIA (1 μM, 56.7 ± 2%). 4. Studies utilizing combinations of Ca2+-channel antagonists suggests that in the rat striatum, two relatively distinct pools of glutamate, released by activation of either P or Q-type Ca2+-channels, exist. In contrast, in the primate there is much overlap between the glutamate released by P and Q-type Ca2+-channel activation. 5. Studies using combinations of enadoline and the Ca2+-channel antagonists suggest that enadoline-induced inhibition of glutamate release occurs primarily via reduction of Ca2+-influx through P-type Ca2+-channels in the rat but via N-type Ca2+-channels in the marmoset. 6. In conclusion, the results presented suggest that there are species differences in the control of glutamate release by κ-opioid receptors and Ca2+-channels.