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Brain Res. 1998 Feb 2;783(1):77-84.

The cannabinoid agonist Win55,212-2 inhibits calcium channels by receptor-mediated and direct pathways in cultured rat hippocampal neurons.

Author information

1
Department of Pharmacology, University of Minnesota Medical School, 3-249 Millard Hall, 435 Delaware St. SE, Minneapolis, MN 55455, USA.

Abstract

The effects of the cannabinoid receptor agonist Win55,212 on Ca2+ channels were studied in rat hippocampal neurons grown in primary culture. Win55,212-2 inhibited whole-cell Ba2+ currents through Ca2+ channels by both CB1 receptor-mediated and direct mechanisms. The concentration dependent inhibition of the current showed two clear phases, a high-affinity receptor-mediated phase (IC50=14+/-2 nM) that was stereoselective and sensitive to a CB1 receptor antagonist, 300 nM SR141716, and a non-saturating phase that was neither stereoselective nor inhibited by SR141716. These concentration-dependent effects were paralleled by Win55212-induced inhibition of glutamatergic synaptic transmission. Win55,212-2 (100 nM) inhibited both omega-agatoxin IVA- and omega-conotoxin GVIA-sensitive currents. Thus, activation of cannabinoid receptors inhibits N- and P/Q-type Ca2+ channels. Activation of cannabinoid receptors inhibited only a fraction of the whole-cell Ca2+ channel current (17+/-2%) even though more than half of the whole-cell Ba2+ current was carried by N- and P/Q-type Ca2+ channels. Concentrations of agonist greater than 1 microM inhibited Ca2+ channels directly.

PMID:
9479052
[Indexed for MEDLINE]

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