Epithelial P2X purinergic receptor channel expression and function
Amanda L. Taylor, Lisa M. Schwiebert, Jeffrey J. Smith, Chris King, Julie R. Jones, Eric J. Sorscher, Erik M. Schwiebert
Amanda L. Taylor, Lisa M. Schwiebert, Jeffrey J. Smith, Chris King, Julie R. Jones, Eric J. Sorscher, Erik M. Schwiebert
View: Text | PDF
Article

Epithelial P2X purinergic receptor channel expression and function

Abstract

P2X purinergic receptor (P2XR) channels bind ATP and mediate Ca2+ influx — 2 signals that stimulate secretory Cl– transport across epithelia. We tested the hypotheses that P2XR channels are expressed by epithelia and that P2XRs transduce extracellular ATP signals into stimulation of Cl– transport across epithelia. Electrophysiological data and mRNA analysis of human and mouse pulmonary epithelia and other epithelial cells indicate that multiple P2XRs are broadly expressed in these tissues and that they are active on both apical and basolateral surfaces. Because P2X-selective agonists bind multiple P2XR subtypes, and because P2X agonists stimulate Cl– transport across nasal mucosa of cystic fibrosis (CF) patients as well as across non-CF nasal mucosa, P2XRs may provide novel targets for extracellular nucleotide therapy of CF.

Authors

Amanda L. Taylor, Lisa M. Schwiebert, Jeffrey J. Smith, Chris King, Julie R. Jones, Eric J. Sorscher, Erik M. Schwiebert

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Apical P2X agonists stimulate ISCCl in an additive manner across human n...
Apical P2X agonists stimulate ISCCl in an additive manner across human non-CF airway epithelial monolayers grown in primary culture. Mean ± SEM of 3 recordings performed on human non-CF airway epithelial monolayers grown in primary culture. A cocktail containing forskolin, IBMX, and cAMP analogue (cAMP) was added as a positive control to stimulate CFTR-dependent ISC and to confirm the integrity of each monolayer. Bumetanide blocked approximately 90% of the stimulated secretory Cl– current. The residual current may be amiloride-insensitive Na+ absorptive current (perhaps P2XR current itself). All effects of inhibitors and agonists were significant (P < 0.05).