Figure 5.

Schematic presentation of effect of various P2Y receptors’ activation on endothelial barrier function. Activation of P2Y₁ receptor stabilises while chronic activation of P2Y₂, P2Y₄, and P2Y₆ receptors results in atherosclerosis. Loss of endothelial barrier integrity is one of the early features of development of atherosclerotic plaques. The molecular mechanisms are not clear yet. P2Y₁₂ receptor is G_i-linked and its activation results in inhibition of adenylyl cyclase (AC) and reduction in intracellular cAMP content that leads to endothelial barrier destabilisation. The P2Y₁₁ is G_s-linked and its activation would lead to opposite effects and endothelial barrier stabilisation. The effects of P2Y₁₁ are hypothetical based on available information about the P2Y₁₁ receptor. Black solid arrows indicate sequence of signalling, broken arrows indicate multiple steps in between, green arrow shows increase in cellular cAMP levels, and red arrows indicate signalling via Gi leading to reduction in cAMP and endothelial barrier disruption. Red blocks mean inhibition.