P2X purinergic receptor (P2XR) channels bind ATP and mediate Ca2+ influx -
2 signals that stimulate secretory Cl- transport across epithelia. We teste
d the hypotheses that P2XR channels are expressed by epithelia and that P2X
Rs transduce extracellular ATP signals into stimulation of Cl- transport ac
ross epithelia. Electrophysiological data and mRNA analysis of human and mo
use pulmonary epithelia and other epithelial cells indicate that multiple P
2XRs are broadly expressed in these tissues and that they are active on bot
h apical and basolateral surfaces. Because P2X-selective agonists bind mult
iple P2XR subtypes, and because P2X agonists stimulate C-l- transport acros
s nasal mucosa of cystic fibrosis (CF) patients as well as across non-CF na
sal mucosa, P2XRs may provide novel targets for extracellular nucleotide th
erapy of CF.