Fig. 2.

Partial hepatectomy stimulates anandamide production through a pathway involving conjugation of arachidonic acid and ethanolamine by FAAH. The generated anandamide, which may cross the cellular membrane either by passive diffusion (dotted arrow) or through a specific transporter [putative anandamide transporter (AT), solid arrow], promotes hepatocytes regeneration through activation of both CB₁ (as shown by Mukhopadhyay et al.) (6) and CB₂ (as shown by Teixeira-Clerc et al.) (16). After CB₁ receptor activation, anandamide induces the forkhead-box M1 (FoxM1) transcriptor factor, which is involved in mitotic progression. The CB₁-mediated induction of FoxM1 involves the Akt/PTEN (protein kinase B/phosphatase and tensin homolog deleted on chromosome 10) signaling pathway. The intracellular mechanisms associated with CB₂-stimulated cell proliferation have been not studied to date. Note that anandamide could stimulate liver regeneration as a paracrine (as shown in this figure) and/or an autocrine lipid mediator. GP-AEA, glycerophospho-anandamide; NArPE, N-arachidonoyl phosphatidylethanolamine.