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ATP and purinergic receptor–dependent membrane traffic in bladder umbrella cells
Edward C.Y. Wang, … , Lori A. Birder, Gerard Apodaca
Edward C.Y. Wang, … , Lori A. Birder, Gerard Apodaca
Published September 1, 2005
Citation Information: J Clin Invest. 2005;115(9):2412-2422. https://doi.org/10.1172/JCI24086.
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Categories: Research Article Cell biology

ATP and purinergic receptor–dependent membrane traffic in bladder umbrella cells

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Abstract

The umbrella cells that line the bladder are mechanosensitive, and bladder filling increases the apical surface area of these cells; however, the upstream signals that regulate this process are unknown. Increased pressure stimulated ATP release from the isolated uroepithelium of rabbit bladders, which was blocked by inhibitors of vesicular transport, connexin hemichannels, ABC protein family members, and nucleoside transporters. Pressure-induced increases in membrane capacitance (a measure of apical plasma membrane surface area where 1 μF ≈ 1 cm2) were inhibited by the serosal, but not mucosal, addition of apyrase or the purinergic receptor antagonist PPADS. Upon addition of purinergic receptor agonists, increased capacitance was observed even in the absence of pressure. Moreover, knockout mice lacking expression of P2X2 and/or P2X3 receptors failed to show increases in apical surface area when exposed to hydrostatic pressure. Treatments that prevented release of Ca2+ from intracellular stores or activation of PKA blocked ATPγS-stimulated changes in capacitance. These results indicate that increased hydrostatic pressure stimulates release of ATP from the uroepithelium and that upon binding to P2X and possibly P2Y receptors on the umbrella cell, downstream Ca2+ and PKA second messenger cascades may act to stimulate membrane insertion at the apical pole of these cells.

Authors

Edward C.Y. Wang, Jey-Myung Lee, Wily G. Ruiz, Elena M. Balestreire, Maximilian von Bodungen, Stacey Barrick, Debra A. Cockayne, Lori A. Birder, Gerard Apodaca

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Figure 1

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ATP localization, release, and hydrolysis in uroepithelium. (A and B) Pr...
ATP localization, release, and hydrolysis in uroepithelium. (A and B) Pressure-induced release of ATP from the serosal (A) or mucosal (B) surfaces of rabbit uroepithelium. The epithelial tissue was mounted in modified Ussing stretch chambers, equilibrated, and pretreated with the indicated drug 15 minutes before the start of the experiment. ATP release was measured just prior to the start of the experiment (background [BKG]), immediately following the rise in hydrostatic pressure (t = 0), and 3, 6, 10, 20, 30, 50, and 60 minutes after the pressure was raised. Results are expressed as mean ± SEM (n ≥ 3). *Statistically significant difference (P < 0.05) relative to the appropriate control. (C) Rabbit uroepithelium was incubated with 5 μM quinacrine for 30 minutes at room temperature, subsequently labeled with FM4-64 (to label cell membranes), and then imaged using a confocal microscope. The image is a projection of the Z series. Quinacrine staining is shown in green, and FM4-64 staining is shown in blue. (D) ATP (50 μM) was added to the mucosal or serosal hemichamber (labeled “Mucosal” and “Serosal,” respectively) of tissue mounted in Ussing stretch chambers. In control reactions, tissue was replaced with plastic film (labeled “Mucosal control” and “Serosal control”). At the designated time points, samples were taken, and the ATP concentration remaining in the hemichamber was measured. Results are expressed as mean ± SEM (n ≥ 3). *Statistically significant difference (P < 0.05) relative to the appropriate control.
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