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pubmed-article:9351889pubmed:abstractTextPrevious work from this laboratory has shown that apical membrane sodium channel activity is stimulated by serosal hyposmotic solutions (Wills, Millinoff & Crowe, 1991). In the present study, we determined whether this stimulation of sodium transport is additive with the actions of prostaglandin E2 (PGE2) or cyclic AMP (cAMP). Addition of exogenous PGE2 (100 nM; serosal bath) to isosmotic solutions led to large increases in the amiloride-sensitive short-circuit current (Isc) and transepithelial conductance (Gt), whereas no significant effects of PGE2 were observed in hyposmotic serosal solutions. Subsequent addition of mucosal amiloride reduced Isc by approximately 95% and Gt by approximately 60%. Inhibition of endogenous PGE2 production by blockers of phospholipase A2 activity (quinacrine or 3[4-octadecyl]-benzoylacrylic acid; OBBA), or inhibition of cyclooxygenase activity by indomethacin reduced the stimulation of Isc and Gt by hyposmotic solutions. Addition of forskolin (FSK) or 3-Isobutyl-1-methylxanthine (IBMX) also resulted in approximately twofold increases in the amiloride-sensitive Isc and Gt and abolished the effects of subsequent hyposmotic challenge. The effects of forskolin, PGE2, and hyposmotic challenge were diminished by pretreatment with H89, a protein kinase A (PKA) inhibitor. We conclude that osmotic regulation of sodium channel activity interacts with multiple intracellular signaling pathways, specifically the arachidonic acid metabolic pathway and the cAMP/PKA intracellular messenger cascade.lld:pubmed
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pubmed-article:9351889pubmed:dateRevised2007-11-15lld:pubmed
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pubmed-article:9351889pubmed:articleTitleOsmotic regulation of Na+ transport across A6 epithelium: interactions with prostaglandin E2 and cyclic AMP.lld:pubmed
pubmed-article:9351889pubmed:affiliationDepartment of Physiology & Biophysics, University of Texas Medical Branch, Galveston 77555, USA.lld:pubmed
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pubmed-article:9351889pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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