INHIBITION BY ANANDAMIDE OF GAP-JUNCTIONS AND INTERCELLULAR CALCIUM SIGNALING IN STRIATAL ASTROCYTES

ANANDAMIDE, an endogenous arachidonic acid derivative that is released from neurons and activates cannabinoid receptors(1), may act as a tra nscellular cannabimimetic messenger in the central nervous system(2-4) . The biological actions of anandamide and the identity of its target cells are, however, still poorly documented(5). Here we show that anan damide is a potent inhibitor of gap-junction conductance and dye perme ability in striatal astrocytes. This inhibitory effect is specific for anandamide as compared to coreleased congeners(4) or structural analo gues, is sensitive to pertussis toxin and to protein-alkylating agents , and is neither mimicked by cannabinoid-receptor agonists nor prevent ed by a cannabinoid-receptor antagonist. Glutamate released from neuro ns evokes calcium waves in astrocytes(6) that propagate via gap juncti ons(7-9), and may, in turn, activate neurons distant from their initia tion sites in astrocytes(10-12). We find that anandamide blocks the pr opagation of astrocyte calcium waves generated by either mechanical st imulation or local glutamate application. Thus, by regulating gap-junc tion permeability, anandamide may control intercellular communication in astrocytes and therefore neuron-glial interactions.