TY - JOUR
T1 - Regulation of ion transport via apical purinergic receptors in intact rabbit airway epithelium
AU - Poulsen, Asser Nyander
AU - Klausen, Thomas Levin
AU - Pedersen, Peter Steen
AU - Willumsen, Niels Johannes
AU - Frederiksen, Ole
N1 - Keywords: Adenosine; Adenosine Triphosphate; Amiloride; Animals; Calcium; Chlorides; Electric Conductivity; Female; Ion Transport; Ionomycin; Membrane Potentials; Nasal Mucosa; Rabbits; Receptors, Purinergic; Receptors, Purinergic P1; Receptors, Purinergic P2; Sodium; Uridine Triphosphate
PY - 2005
Y1 - 2005
N2 - We investigated purinergic receptors involved in ion transport regulation in the intact rabbit nasal airway epithelium. Stimulation of apical membrane P2Y receptors with ATP or UTP (200 microM) induced transient increases in short-circuit current (Isc) of 13 and 6% followed by sustained inhibitions to 8 and 17% below control level, respectively. Serosal application of nucleotides had no effect. The ATP-induced response appeared to involve additional activation of apical adenosine (P1) and P2X receptors. The inhibitory effect of ATP and UTP on Isc was eliminated by pretreatment with amiloride (100 microM), while the stimulatory effect was potentiated, indicating that ATP and UTP inhibit Na+ and stimulate Cl- current. Ionomycin (1 microM) induced responses similar to UTP and ATP and desensitized the epithelium to the nucleotides, indicating involvement of intracellular Ca2+ (Ca2+ i. Furthermore, ATP, UTP and ionomycin induced 21, 24, and 21% decreases, respectively, in transepithelial conductance. Measurements of unidirectional isotope fluxes showed a 39% decrease in the dominant net Na+ absorption in response to ATP, while the smaller net Cl- secretion increased only insignificantly and unidirectional Cl- fluxes decreased significantly. The results suggest that nucleotides released to the airway surface liquid exert an autocrine regulation of epithelial NaCl absorption mainly by inhibiting the amiloride-sensitive epithelial Na+ channel (ENaC) and paracellular anion conductance via a P2Y receptor-dependent increase in Ca2+ i, while stimulation of Cl- secretion is of minor importance.
AB - We investigated purinergic receptors involved in ion transport regulation in the intact rabbit nasal airway epithelium. Stimulation of apical membrane P2Y receptors with ATP or UTP (200 microM) induced transient increases in short-circuit current (Isc) of 13 and 6% followed by sustained inhibitions to 8 and 17% below control level, respectively. Serosal application of nucleotides had no effect. The ATP-induced response appeared to involve additional activation of apical adenosine (P1) and P2X receptors. The inhibitory effect of ATP and UTP on Isc was eliminated by pretreatment with amiloride (100 microM), while the stimulatory effect was potentiated, indicating that ATP and UTP inhibit Na+ and stimulate Cl- current. Ionomycin (1 microM) induced responses similar to UTP and ATP and desensitized the epithelium to the nucleotides, indicating involvement of intracellular Ca2+ (Ca2+ i. Furthermore, ATP, UTP and ionomycin induced 21, 24, and 21% decreases, respectively, in transepithelial conductance. Measurements of unidirectional isotope fluxes showed a 39% decrease in the dominant net Na+ absorption in response to ATP, while the smaller net Cl- secretion increased only insignificantly and unidirectional Cl- fluxes decreased significantly. The results suggest that nucleotides released to the airway surface liquid exert an autocrine regulation of epithelial NaCl absorption mainly by inhibiting the amiloride-sensitive epithelial Na+ channel (ENaC) and paracellular anion conductance via a P2Y receptor-dependent increase in Ca2+ i, while stimulation of Cl- secretion is of minor importance.
U2 - 10.1007/s00424-005-1388-4
DO - 10.1007/s00424-005-1388-4
M3 - Journal article
C2 - 15822001
SN - 0031-6768
VL - 450
SP - 227
EP - 235
JO - Pflügers Archiv - European Journal of Physiology
JF - Pflügers Archiv - European Journal of Physiology
IS - 4
ER -