Extracellular Purines in Endothelial Cell Barrier Regulation - Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function - page 39

Table 3.1 The family of purinoceptors

of A1, A2A, A2B, A3, P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11 purinoceptors
had been demonstrated [2, 77, 85, 103, 106]. Our recent study (data not shown)
indicates the expression of P2Y13 in human pulmonary artery EC (HPAEC).
Heterotrimeric G-proteins activated by P1 and P2Y receptors in EC belong to four
functionally distinct subfamilies: G 12/13. Activation of

these particular G-proteins determines a cell response upon agonist stimulation. In
this review, we are mainly focused on the effects of purine-induced P1 and P2Y
receptors on modulation of endothelial monolayer integrity, respective signaling
pathways leading to an enhancement or to a loss of endothelial barrier function will
be discussed. Several studies demonstrated that P2X receptors are abundant in EC
[106, 108, 112]. However, the P2X specific agonist, AMP-CCP, was completely
inactive on the HPAEC monolayer [54] suggesting that P2X receptors are unlikely
to be involved in ATP-mediated EC barrier enhancement.

α s, G α q/11, G α i and G α

3.2 Purinoceptor-Mediated Regulation of Endothelial Barrier
Function

3.2.1 Cell Signaling Pathways Activated Upon Purinoceptor
Stimulation

Integrity of endothelium is determined by cell-cell and cell-matrix contacts, as
well as by organization of cytoskeleton of EC. Signaling cascades are activated
by ligand-bound purinoceptors. Dynamic changes in cytoskeleton organization and
proteins link cytoskeletal structures to adherens junctions (AJ), tight junctions (TJ),
and focal adhesion (FA) contacts. These are key targets of purinoceptor-mediated
signaling pathways affecting endothelial barrier function. A major role in endothe-
lial cell-cell contacts belong to the AJ and its transmembrane protein, vascular