Inhibition by anandamide of gap junctions and intercellular calcium signalling in striatal astrocytes

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Abstract
ANANDAMIDE, an endogenous arachidonic acid derivative that is released from neurons and activates cannabinoid receptors1, may act as a transcellular cannabimimetic messenger in the central nervous system2–4. The biological actions of anandamide and the identity of its target cells are, however, still poorly documented5. Here we show that anandamide is a potent inhibitor of gap-junction conductance and dye permeability in striatal astrocytes. This inhibitory effect is specific for anandamide as compared to co-released congeners4 or structural analogues, is sensitive to pertussis toxin and to protein-alkylating agents, and is neither mimicked by cannabinoid-receptor agonists nor prevented by a cannabinoid-receptor antagonist. Glutamate released from neurons evokes calcium waves in astrocytes6 that propagate via gap junctions7–9, and may, in turn, activate neurons distant from their initiation sites in astrocytes10–12. We find that anandamide blocks the propagation of astrocyte calcium waves generated by either mechanical stimulation or local glutamate application. Thus, by regulating gap-junction permeability, anandamide may control intercellular communication in astrocytes and therefore neuron–glial interactions.