Key result
P2Y receptor activation reduces human vascular endothelial cell size by ~14% and enhances macromolecular permeability.
Why the study?
The effects of P2-receptor agonists on cell size, intracellular calcium levels, and permeability in human vascular endothelial cells were investigated to understand their role in endothelial function.
Absolute Event Rate: 86% vs 100%
p-value: p=<0.05
Activation of P2Y receptors in human vascular endothelial cells decreases cell size and increases intracellular calcium, facilitating macromolecular permeability.
May enhance endothelial permeability via P2Y signaling; leaves open in vivo relevance and therapeutic targeting.
We investigated the effects of P2-receptor agonists on cell size, intracellular calcium levels ([Ca(2+)](i)), and permeation of FITC-labeled dextran (FD-4) as well as the relationship between these effects in human umbilical vein endothelial cells (HUVEC). FD-4 concentration, cell size, and [Ca(2+)](i) were analyzed by HPLC with fluorescence, phase contrast microscopic imaging, and fluorescent confocal microscopic imaging, respectively. The P2Y(1)-receptor agonists 2-methylthio ATP (2meS-ATP) and ADP decreased cell size and increased [Ca(2+)](i) in HUVEC. The P2Y(2)-receptor agonist UTP increased [Ca(2+)](i), but did not influence cell size. The P2X-receptor agonist alpha,beta-methylene ATP did not induce either response. The decrease in size and increase in [Ca(2+)](i) by 2meS-ATP were blocked by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, P2Y(1)-antagonist), thapsigargin (Ca(2+)-pump inhibitor), and U73122 (phospholipase C inhibitor). Furthermore, 2meS-ATP (P2Y(1)-receptor agonist) enhanced permeation of FD-4 through the endothelial cell monolayer. The 2meS-ATP-induced enhancement of the permeation was also prevented by PPADS, thapsigargin, and U73122. These results indicate that activation of P2Y receptors induces a decrease in cell size, an increase in [Ca(2+)](i), and may participate in facilitating macromolecular permeability in HUVEC.
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Tanaka et al. (2004) studied this question. 2-methylthio ATP (2meS-ATP) vs. Baseline (before addition) was evaluated on Cell size relative to baseline (p=<0.05). Activation of P2Y receptors by 10 μM 2meS-ATP significantly decreased human vascular endothelial cell size to 86% of baseline, increased intracellular calcium, and enhanced macromolecular permeability.
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