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  • Title: Cannabinoids inhibit the release of [3H]glutamate from rodent hippocampal synaptosomes via a novel CB1 receptor-independent action.
    Author: Köfalvi A, Vizi ES, Ledent C, Sperlágh B.
    Journal: Eur J Neurosci; 2003 Oct; 18(7):1973-8. PubMed ID: 14622229.
    Abstract:
    In this study we investigated the effect of cannabinoids on [3H]glutamate release from hippocampal synaptosomes of rat and CB1-null mutant mouse. In the rat, cannabinoid receptor agonists, i.e. CP55,940 (EC50, 0.84 microm), WIN55,212-2 (EC50, 3.47 microm), ACEA (EC50, 17.8 microm), and R-(+)-methanandamide (EC50, 19.8 microm) concentration-dependently inhibited the 25-mm-K+ depolarization-evoked release of [3H]glutamate and, among them, WIN55,212-2 displayed the greatest efficacy. The CB1 receptor antagonists SR141716A (1-5 microm) and AM251 (1 microm) and the VR1 vanilloid receptor antagonist capsazepine (10 microm) did not antagonize the effect of the agonists. SR141716A by itself attenuated the evoked [3H]glutamate release. WIN55,212-2 inhibited the release of [3H]glutamate in CB1 -/- mice as well. These data demonstrate that the action of cannabinoids on glutamate release in the hippocampus is pharmacologically distinct and independent from the cloned CB1 receptor.
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