Figure 1: Regulation of adenosine triphosphate binding cassette transporter A1 (ABCA1) expression by adenosine. Methotrexate via numerous steps (jagged arrow) results in increased levels of adenosine. Adenosine activates the G-protein coupled receptor, A2A, inducing an increase in adenylyl cyclase activity. The subsequent rise in cyclic adenosine monophosphate (cAMP) activates protein kinase A (PKA) which phosphorylates the cAMP response element-binding protein (CREB). CREB then translocates into the nucleus where it upregulates ABCA1 gene expression.