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

1 The modulation of depolarization (4-aminopyridine, 2 mM)-evoked endogenous glutamate release by kappa-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 kappa-opioid receptor agonist, in a concentration-dependent and nor-binaltorphimine (nor-BNI, selective kappa-opioid receptor antagonist)-sensitive manner in rat (IC50=4.4+/-0.4 mu M) and marmoset (IC50=2.9+/-0.7 mu M) striatal synaptosomes. However, in the marmoset, there was a significant (approximate to 23%) nor-BNI-insensitive component. 3 In rat striatal synaptosomes, the Ca2+-channel antagonists omega-agatoxin-IVA (P/Q-type blocker), omega-conotoxin-MVIIC (N/P/Q-type blocker) and omega-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 omega-agatoxin-IVA (30 nM, 57.6+/-2.3%, inhibition), omega-conotoxin-MVIIC (300 nM, 57.8+/-3.1%) and omega-conotoxin-GVIA (1 mu M, 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 ria 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 li-opioid receptors and Ca2+-channels.