title: Control of glutamate release by calcium channels and kappa-opioid receptors in rodent and primate striatum.
abstract: 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. 4-Aminopyridine (4-AP)-stimulated, Ca2+ -dependent glutamate release was inhibited by enadoline, a selective kappa-opioid receptor agonist, in a concentration-dependent and norbinaltorphimine (nor-BNI, selective kappa-opioid receptor antagonist)-sensitive manner in rat (IC50 = 4.4+/-0.4 microM) and marmoset (IC50 = 2.9+/-0.7 microM) striatal synaptosomes. However, in the marmoset, there was a significant (approximately 23%) nor-BNI-insensitive component. 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 microM, 56.7+/-2%). 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. 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. In conclusion, the results presented suggest that there are species differences in the control of glutamate release by kappa-opioid receptors and Ca2+ -channels.
authors.affiliation: Manchester Movement Disorders Laboratory, Division of Neuroscience, School of Biological Sciences, University of Manchester. m.hill@man.ac.uk
authors.forename: M P
authors.initials: MP
authors.lastname: Hill
authors.forename: J M
authors.initials: JM
authors.lastname: Brotchie
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002144:Callithrix; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010455:Peptides / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
chemical_list: D001572:Benzofurans; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009292:Narcotic Antagonists; D010455:Peptides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; C051844:norbinaltorphimine; D018698:Glutamic Acid; D013779:Tetrodotoxin; D009271:Naltrexone; D020866:omega-Conotoxin GVIA; D015761:4-Aminopyridine; C067110:enadoline