Epithelial P2X purinergic receptor channel expression and function

Sustained Calcium Entry through P2X Nucleotide Receptor Channels in Human Airway Epithelial Cells

“…These stimulations occurred in Na ϩ -rich solutions (27). Despite this knowledge, we did not perform experiments designed to examine P2XR-mediated signaling in this study (27) 3 ; however, responses to both BzBzATP and ATP were much more profound under Na ϩ -free conditions.…”

“…In a past study (27), our laboratory showed that a P2X-selective agonist, BzBzATP, stimulated transepithelial chloride secretion in Ussing chamber experiments on airway epithelia that had both transient and sustained components and in nasal potential difference assays on mouse nasal mucosa that were transient stimulations that averaged 1-2 mV. These stimulations occurred in Na ϩ -rich solutions (27).…”

“…Experiments described below lend clarification to these early data. [Ca 2ϩ ] i in the Presence of Extracellular Na ϩ and Ca 2ϩ -Multiple subtypes of P2X receptors have already been described in human, rabbit, and rodent airway epithelial cells (27,34,35). Thus, we speculated that the higher peak in [Ca 2ϩ ] i in the presence of extracellular Ca 2ϩ and the loss of the full response in Ca 2ϩ -free extracellular solution could be explained by the concomitant activation of P2X receptors activated by ATP.…”

“…P2Y receptors couple to heterotrimeric G proteins and phospholipases (primarily phospholipase C␤) to raise intracellular free calcium concentration (26). In CF epithelial cells from multiple tissues, expression of P2X and P2Y receptors appears unaffected, offering the possibility to increase [Ca 2ϩ ] i through targeting a naturally expressed receptor in the apical or basolateral membrane domains (27,28). Nonetheless, in different CF epithelial cell models, the desensitization of P2Y receptors and the transient nature of the Ca 2ϩ response upon chronic and repeated delivery of a P2Y-specific agonist have made it difficult to generate stable stimuli for ion secretion (7,29).…”

ENaC, renal sodium excretion and extracellular ATP

“…It is now widely accepted that released ATP can act as a local hormone on both sides of the kidney tubule, where this molecule has ample choices for molecular targets. The presence of almost all of the molecularly identified subtypes of ionotropic (P2X) and metabotropic (P2Y) receptors for ATP has been demonstrated in the apical and/or basolateral membranes of native epithelial cells and immortalised epithelial cell lines [7,17,[27][28][29]. Ionotropic P2X receptors are represented by homomeric assemblies (P2X 1,2,3,4,5,6,7 ) and heteromeric assemblies (P2X 1/2 , P2X 1/4 , P2X 1/5 , P2X 2/3 , P2X 2/6 , P2X 4/6 , P2X 4/7 ).…”