(R)-methanandamide inhibits receptor-induced calcium responses by depleting internal calcium stores in cultured astrocytes.

The effect of (R)-methandamide, a chiral analog of the endogenous cannabimimetic anandamide, was investigated on calcium signalling in cultured rat astrocytes loaded with Indo-1. Pretreatment of astrocytes with (R)-methandamide resulted in the inhibition of calcium responses induced by endothelin-1 or glutamate. Test of the filling level of internal calcium stores and biochemical assays of phospholipase C activity suggested that this inhibition resulted from the depletion of internal pools. This effect occurred in a reversible time- and dose-dependent 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 analog of anandamide controls calcium signalling in astrocytes through a PTX-sensitive mechanism which leads to the depletion of fast mobilizable internal stores.