(R)-METHANANDAMIDE INHIBITS RECEPTOR-INDUCED CALCIUM RESPONSES BY DEPLETING INTERNAL CALCIUM STORES IN CULTURED ASTROCYTES

The effect of (R)-methanandamide, a chiral analog of the endogenous ca nnabimimetic anandamide, was investigated on calcium signalling in cul tured rat astrocytes loaded with Indo-1. Pretreatment of astrocytes wi th (R)-methanandamide resulted in the inhibition of calcium responses induced by endothelin-1 or glutamate. Test of the filling level of int ernal calcium stores and biochemical assays of phospholipase C activit y suggested that this inhibition resulted from the depletion of intern al pools. This effect occurred in a reversible time- and dose-dependen t manner, and was prevented by treating the cells with pertussis toxin (PTX) but was not reproduced by similar concentrations of arachidonic acid. Altogether, these observations demonstrate that this stable ana log of anandamide controls calcium signalling in astrocytes through a PTX-sensitive mechanism which leads to the depletion of fast mobilizab le internal stores.