Zusammenfassung
In airways Cl- secretion is activated and Na+ absorption is inhibited when P2Y(2) receptors are stimulated by ATP or UTP. Both nucleotides are subject to degradation to ADP and UDP by ecto-nucleoticlases. Here we show that these metabolites change electrolyte transport by stimulation of P2Y(6) receptors in mouse trachea. Immunohistochemistry confirmed luminal and basolateral expression of P2Y(6) ...
Zusammenfassung
In airways Cl- secretion is activated and Na+ absorption is inhibited when P2Y(2) receptors are stimulated by ATP or UTP. Both nucleotides are subject to degradation to ADP and UDP by ecto-nucleoticlases. Here we show that these metabolites change electrolyte transport by stimulation of P2Y(6) receptors in mouse trachea. Immunohistochemistry confirmed luminal and basolateral expression of P2Y(6) receptors. In Ussing chamber experiments luminal ADP, UDP or the P2Y(6) receptor agonist INS48823 induced both transient and persistent increase in short circuit currents (I-sc). Activation of I-SC was inhibited by the P2Y(6) receptor blocker PPADS. The transient response was inhibited by DIDS, whereas the persistent ISC was inhibited by glibenclamide and by the protein kinase A (PKA) blocker H-89. Moreover, sustained activation of ISC by luminal UDP was inhibited by blocking basolateral K+ channels with 293B. Possible effects of diphosphates on P2Y(1) or adenosine receptors were excluded by the inhibitors MRS2179 and 8-SPT, respectively. Inhibition of amiloride sensitive Na+ absorption was only seen after blocking basolateral K+ channels with 293B. In contrast, Cl- secretion activated by basolateral ADP or UDP was only transient and was blocked by the sk4 K+ channel blocker clotrimazole. In summary, activation of luminal P2Y(6) receptors in the airways shifts electrolyte transport towards secretion by increasing intracellular Ca2+ and activation of PKA. Copyright (C) 2005 S. Karger AG, Basel.
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