Regulation of endothelial AMT by E2 and cross-talk with platelets.
Binding of E2 to an endothelial ESR triggers elevation of intracellular calcium, which leads to increased activity of PLD, 15-LOX, and NOS. Activation of PLD enhances the release of AEA from membrane phospholipid precursors, whereas activation of NOS stimulates AMT and activation of 15-LOX inhibits AEA hydrolysis by FAAH. Taken together, E2 stimulates the release of AEA from endothelial cells. Binding of AEA itself, or of 2-AG released from platelets, to type 1 cannabinoid receptors (CB1R) of endothelial cells further potentiates AEA release. E2 also binds to an intracellular receptor (E2R) in platelets, thus preventing IP3 elevation and cAMP reduction induced by binding of ADP to its receptors (ADPRs). On the other hand, AEA inhibits ADP-induced release of 5-HT from platelets.
