Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation

Figure 1

Cannabinoid receptor signal transduction pathway. Upon cannabinoid receptor engagement by a cannabinoid, the activated α subunit inhibits adenylate cyclase activity causing a decrease in cAMP, which, in turn, decreases PKA activity. The βγ dimer activates PI3K, which, in turn, activates PLC that ultimately leads to increased intracellular calcium levels. PI3K can active the MAPK pathways. Akt may lead to mTORC1 activation. The βγ dimer can, also, activate MKK leading to activation of the MAPK pathways. CB: cannabinoid; CB1R: cannabinoid type 1 receptor; CB2R: cannabinoid type 2 receptor; AC: adenylate cyclase; PKA: protein kinase A; PI3K: phosphatidylinositol-3 kinase; PLC: phospholipase C; IP₃: inositol trisphosphate; mTORC1: mammalian target of rapamycin complex 1; MKK: mitogen-activated protein kinase kinases; MAPK: mitogen-activated protein kinase; JNK: Jun kinases; Erk: extracellular signal-regulated kinases.