Effects of purinergic stimulation, CFTR and osmotic stress on amiloride-sensitive Na+ transport in epithelia and Xenopus oocytes.
Both stimulation of purinergic receptors by ATP and activation of the cystic fibrosis transmembrane conductance regulator (CFTR) inhibit amiloride-sensitive Na+ transport and activate Cl- secretion. These changes in ion transport may well affect cell volume. We therefore examined whether cell shrinkage or cell swelling do affect amiloride-sensitive Na+ transport in epithelial tissues or Xenopus oocytes and whether osmotic stress interferes with regulation of Na+ transport by ATP or CFTR. Stimulation of purinergic receptors by ATP/UTP or activation of CFTR by IBMX and forskolin inhibited amiloride-sensitive transport in mouse trachea and colon, respectively, by a mechanism that was Cl- dependent. When exposed to a hypertonic but not hypotonic bath solution, amiloride-sensitive Na+ transport was inhibited in mouse trachea and colon, independent of the extracellular Cl- concentration. Both inhibition of Na+ transport by hypertonic bath solution and ATP were additive. When coexpressed in Xenopus oocytes, activation of CFTR by IBMX and forskolin inhibited the epithelial Na+ channel (ENaC) in a Cl- dependent fashion. However, both hypertonic and hypotonic bath solutions showed only minor effects on amiloride-sensitive conductance, independent of the bath Cl- concentration. Moreover, CFTR-induced inhibition of ENaC could be detected in oocytes even after exposure to hypertonic or hypotonic bath solutions. We conclude that amiloride-sensitive Na+ absorption in mouse airways and colon is inhibited by cell shrinkage by a mechanism that does not interfere with purinergic and CFTR-mediated inhibition of ENaC.
Schreiber
R
R
Institut für Physiologie, Universität Regensburg, Universitätsstrasse 31, D-93053 Regensburg, Germany.
König
J
J
Sun
J
J
Markovich
D
D
Kunzelmann
K
K
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008353:Mannitol; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009997:Osmotic Pressure / Q000187:drug effects; D011687:Purines; D011983:Receptors, Purinergic / Q000187:drug effects; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012964:Sodium / Q000493:pharmacokinetics*; D012965:Sodium Chloride / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014544:Uridine Triphosphate / Q000494:pharmacology; D014982:Xenopus laevis
D011687:Purines; D011983:Receptors, Purinergic; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D008353:Mannitol; D012965:Sodium Chloride; D000584:Amiloride; D012964:Sodium; D015056:1-Methyl-3-isobutylxanthine; D014544:Uridine Triphosphate; D007213:Indomethacin