Extracellular Purines in Endothelial Cell Barrier Regulation - Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function - page 47

P2Y6 receptor-coupled ion transport [109]. We speculate that extracellular purines
released from the blood cells (for example, platelets), ECs or alveolar epithelial
cells (basal side of EC) stimulate purinergic receptors based on their expression
pattern (apical or basal) as schematically presented (Fig. 3.4). A recent study indi-
cated the hetero-oligomerization between two metabotrofic purinoceptors, P2Y1
and P2Y11, co-expressed in HEK293 cells, promotes agonist-induced internaliza-
tion of the P2Y11 receptor, which itself is unable to undergo endocytosis [30].
Moreover, the agonist profile for the co-expressed P2Y1 and P2Y11 was differ-
ent from the agonist profile established for cells expressing the P2Y11 receptor
only. The hetero-oligomerization of the P2Y1 and P2Y11 receptors modifies the
functions of the P2Y11 receptor in response to extracellular nucleotides. More stud-
ies are needed to characterize the agonist profile of expressed purinoceptors, the
expression profile of multiple purinoceptors on the apical or basal side of EC and
the pathophysiological agonist concentrations that activate various purinoceptors.
Obtained data will help to establish conditions for possible purine therapies.
Fig. 3.4 Possible interaction between extracellular purines and purinoceptors in the endothelium.
The apical and basolateral domains are separated by tight junctions
References
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2. Ahmad S, Ahmad A, White CW. (2006) Purinergic signaling and kinase activation for
survival in pulmonary oxidative stress and disease. Free Radic Biol Med 41:29-40.