Epithelial P2X purinergic receptor channel expression and function.
P2X purinergic receptor (P2XR) channels bind ATP and mediate Ca(2+) 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.
Taylor
A L
AL
Department of Cell Biology, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama-Birmingham, Birmingham, Alabama 35294, USA.
Schwiebert
L M
LM
Smith
J J
JJ
King
C
C
Jones
J R
JR
Sorscher
E J
EJ
Schwiebert
E M
EM
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002034:Bumetanide / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D015342:DNA Probes; D018076:DNA, Complementary; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology; D008099:Liver / Q000502:physiology; D008168:Lung / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D010179:Pancreas / Q000502:physiology; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000502:physiology*; D020545:Respiratory Mucosa / Q000502:physiology; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D015342:DNA Probes; D018076:DNA, Complementary; D020033:Protein Isoforms; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D002034:Bumetanide; D000584:Amiloride; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid