Anandamide is an endogenous ligand for central cannabinoid receptors a
nd is released after neuronal depolarization. Anandamide increased pro
tein tyrosine phosphorylation in rat hippocampal slices and neurons in
culture. The action of anandamide resulted from the inhibition of ade
nylyl cyclase and cyclic adenosine 3',5'-monophosphate-dependent prote
in kinase. One of the proteins phosphorylated in response to anandamid
e was an isoform of pp125-focal adhesion kinase (FAK+) expressed prefe
rentially in neurons. Focal adhesion kinase is a tyrosine kinase invol
ved in the interactions between the integrins and actin-based cytoskel
eton. Thus, anandamide may exert neurotrophic effects and play a role
in synaptic plasticity.