ABSTRACT
Prostaglandins E1 and F2 alpha (PGE1 and PGF2 alpha) stimulate short-circuit current (SCC), tissue conductance (G), and net Cl secretion by canine tracheal mucosa. To determine if these actions of prostaglandins require extracellular Ca we tested the effects of PGE1 and PGF2 alpha on tracheal mucosa mounted in Ussing chambers when one side of the preparation was exposed to 0.2 mM ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid in Krebs-Henseleit solution without Ca. Lack of Ca from the mucosal bath was associated with increased G, lowered potential difference (PD), and severalfold increase of 22Na and 36Cl fluxes in both directions. Addition of 1 microM of PGE1 or PGF2 alpha to the Ca-free mucosal bath raised PD by 6 mV and SCC by 15 microA X cm-2 but decreased G by 1.4 mS X cm-2. Unidirectional 22Na and 36Cl fluxes decreased by 32-49% (n = 7, P less than 0.05). These findings suggest that the increase in G, most likely of the paracellular pathway and brought about by the lack of mucosal Ca, was partially reversible by PGE1 and PGF2 alpha. In contrast, when tissues were exposed to Ca-free solution on their submucosal side, PGE1 or PGF2 alpha were not able to reverse the progressive decline in PD and tissue resistance (n = 8). [14C]mannitol flux increased when Ca was absent from the mucosal bath; then addition of 1 microM PGF2 alpha caused a 37% decline in flux (n = 5). In contrast, the increase in the flux of [14C]mannitol found when the submucosal bath lacked calcium was not reversed by 1 microM PGE1.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Calcium/metabolism , Ion Channels/metabolism , Prostaglandins/metabolism , Trachea/metabolism , Alprostadil , Animals , Biological Transport, Active , Calcium/physiology , Chlorides/metabolism , Dinoprost , Dogs , Electric Conductivity , Intercellular Junctions/metabolism , Mucous Membrane/metabolism , Mucous Membrane/physiology , Prostaglandins E/metabolism , Prostaglandins F/metabolism , Sodium/metabolism , Trachea/physiologyABSTRACT
We tested the effect of prostaglandins PGF2 alpha and PGE1 on the transport of 36Cl and 22Na by canine tracheal epithelium. Sheets of epithelium were mounted in Ussing chambers and short-circuited. Addition of PGF2 alpha to the mucosal side resulted in an increase of net Cl secretion from 0.71 +/- 0.41 to 2.40 +/- 0.67 mu eq . cm-2 . h-1 without significant effect on net Na absorption. Prostaglandin E1 on the mucosal side increased net Cl secretion from 1.36 +/- 0.31 to 2.69 +/- 0.35 and decreased Na absorption from 0.87 +/- 0.16 to 0.49 +/- 0.09. Indomethacin significantly depressed net Cl secretion from 1.36 +/- 0.36 to 0.57 +/- 0.22. Subsequent addition of PGE1 augmented net Cl secretion to 3.88 +/- 0.75. PGE1 did not enhance [14C]mannitol fluxes across this epithelium. Cellular levels of cAMP increased in response to PGE1 from 130 +/- 12.7 to 642 +/- 33.4 pmol . mg prot-1 . 10 min-1, whereas PGF2 alpha had no effect. These data suggest that although effects of PGF2 alpha and PGE1 are similar as pertains to net Cl secretion, they differ in their effects on Na transport and their capacity to increase cAMP levels. Alterations in Cl and Na transport in response to PGE1 are likely to be mediated, at least in part, by the adenylate cyclase-cAMP system. Furthermore, endogenous prostaglandins may have an important regulatory role in ion transport by airways epithelium.
