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. 1985 Mar 1;85(3):409–429. doi: 10.1085/jgp.85.3.409

Cyclic AMP inhibits Na+/H+ exchange at the apical membrane of Necturus gallbladder epithelium

PMCID: PMC2215790  PMID: 2985735

Abstract

The effects of elevating intracellular cAMP levels on Na+ transport across the apical membrane of Necturus gallbladder epithelium were studied by intracellular and extracellular microelectrode techniques. Intracellular cAMP was raised by serosal addition of the phosphodiesterase inhibitor theophylline (3 mM) or mucosal addition of either 8-Br-cAMP (1 mM) or the adenylate cyclase activator forskolin (10 microM). During elevation of intracellular cAMP, intracellular Na+ activity (alpha Nai) and intracellular pH (pHi) decreased significantly. In addition, acidification of the mucosal solution, which contained either 100 or 10 mM Na+, was inhibited by approximately 50%. The inhibition was independent of the presence of Cl- in the bathing media. The rates of change of alpha Nai upon rapid alterations of mucosal [Na+] from 100 to 10 mM and from 10 to 100 mM were both decreased, and the rate of pHi recovery upon acid loading was also reduced by elevated cAMP levels. Inhibition was approximately 50% for all of these processes. These results indicate that cAMP inhibits apical membrane Na+/H+ exchange. The results of measurements of pHi recovery at 10 and 100 mM mucosal [Na+] and a kinetic analysis of recovery as a function of pHi suggest that the main or sole mechanism of the inhibitory effect of cAMP is a reduction in the maximal rate of acid extrusion. In conjunction with the increase in apical membrane electrodiffusional Cl- permeability, produced by cAMP, which causes a decrease in net Cl- entry (Petersen, K.-U., and L. Reuss, 1983, J. Gen. Physiol., 81:705), inhibition of Na+/H+ exchange contributes to the reduction of fluid absorption elicited by this agent. Similar mechanisms may account for the effects of cAMP in other epithelia with similar transport properties. It is also possible that inhibition of Na+/H+ exchange by cAMP plays a role in the regulation of pHi in other cell types.

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Selected References

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  1. Aronson P. S., Nee J., Suhm M. A. Modifier role of internal H+ in activating the Na+-H+ exchanger in renal microvillus membrane vesicles. Nature. 1982 Sep 9;299(5879):161–163. doi: 10.1038/299161a0. [DOI] [PubMed] [Google Scholar]
  2. Baerentsen H., Giraldez F., Zeuthen T. Influx mechanisms for Na+ and Cl- across the brush border membrane of leaky epithelia: a model and microelectrode study. J Membr Biol. 1983;75(3):205–218. doi: 10.1007/BF01871951. [DOI] [PubMed] [Google Scholar]
  3. Bello-Reuss E., Grady T. P., Reuss L. Mechanism of the effect of cyanide on cell membrane potentials in Necturus gall-bladder epithelium. J Physiol. 1981 May;314:343–357. doi: 10.1113/jphysiol.1981.sp013712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bers D. M., Ellis D. Intracellular calcium and sodium activity in sheep heart Purkinje fibres. Effect of changes of external sodium and intracellular pH. Pflugers Arch. 1982 Apr;393(2):171–178. doi: 10.1007/BF00582941. [DOI] [PubMed] [Google Scholar]
  5. Boron W. F., Boulpaep E. L. Intracellular pH regulation in the renal proximal tubule of the salamander. Na-H exchange. J Gen Physiol. 1983 Jan;81(1):29–52. doi: 10.1085/jgp.81.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boron W. F., De Weer P. Intracellular pH transients in squid giant axons caused by CO2, NH3, and metabolic inhibitors. J Gen Physiol. 1976 Jan;67(1):91–112. doi: 10.1085/jgp.67.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Boron W. F., Russell J. M., Brodwick M. S., Keifer D. W., Roos A. Influence of cyclic AMP on intracellular pH regulation and chloride fluxes in barnacle muscle fibers. Nature. 1978 Nov 30;276(5687):511–513. doi: 10.1038/276511a0. [DOI] [PubMed] [Google Scholar]
  8. Dennis V. W. Influence of bicarbonate on parathyroid hormone-induced changes in fluid absorption by the proximal tubule. Kidney Int. 1976 Nov;10(5):373–380. doi: 10.1038/ki.1976.123. [DOI] [PubMed] [Google Scholar]
  9. Diez de los Rios A., DeRose N. E., Armstrong W. M. Cyclic AMP and intracellular ionic activities in Necturus gallbladder. J Membr Biol. 1981;63(1-2):25–30. doi: 10.1007/BF01969442. [DOI] [PubMed] [Google Scholar]
  10. Duffey M. E., Hainau B., Ho S., Bentzel C. J. Regulation of epithelial tight junction permeability by cyclic AMP. Nature. 1981 Dec 3;294(5840):451–453. doi: 10.1038/294451a0. [DOI] [PubMed] [Google Scholar]
  11. Eaton D. C., Hamilton K. L., Johnson K. E. Intracellular acidosis blocks the basolateral Na-K pump in rabbit urinary bladder. Am J Physiol. 1984 Dec;247(6 Pt 2):F946–F954. doi: 10.1152/ajprenal.1984.247.6.F946. [DOI] [PubMed] [Google Scholar]
  12. Ericson A. C., Spring K. R. Coupled NaCl entry into Necturus gallbladder epithelial cells. Am J Physiol. 1982 Sep;243(3):C140–C145. doi: 10.1152/ajpcell.1982.243.3.C140. [DOI] [PubMed] [Google Scholar]
  13. Frizzell R. A., Dugas M. C., Schultz S. G. Sodium chloride transport by rabbit gallbladder. Direct evidence for a coupled NaCl influx process. J Gen Physiol. 1975 Jun;65(6):769–795. doi: 10.1085/jgp.65.6.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Frizzell R. A., Field M., Schultz S. G. Sodium-coupled chloride transport by epithelial tissues. Am J Physiol. 1979 Jan;236(1):F1–F8. doi: 10.1152/ajprenal.1979.236.1.F1. [DOI] [PubMed] [Google Scholar]
  15. Kinsella J. L., Aronson P. S. Amiloride inhibition of the Na+-H+ exchanger in renal microvillus membrane vesicles. Am J Physiol. 1981 Oct;241(4):F374–F379. doi: 10.1152/ajprenal.1981.241.4.F374. [DOI] [PubMed] [Google Scholar]
  16. Kinsella J. L., Aronson P. S. Properties of the Na+-H+ exchanger in renal microvillus membrane vesicles. Am J Physiol. 1980 Jun;238(6):F461–F469. doi: 10.1152/ajprenal.1980.238.6.F461. [DOI] [PubMed] [Google Scholar]
  17. Lea T. J., Ashley C. C. Carbon dioxide or bicarbonate ions release Ca2+ from internal stores in crustacean myofibrillar bundles. J Membr Biol. 1981;61(2):115–125. doi: 10.1007/BF02007638. [DOI] [PubMed] [Google Scholar]
  18. Petersen K. U., Osswald H., Heintze K. Asymmetric release of cyclic AMP from guinea-pig and rabbit gallbladder. Naunyn Schmiedebergs Arch Pharmacol. 1982 Mar;318(4):358–362. doi: 10.1007/BF00501178. [DOI] [PubMed] [Google Scholar]
  19. Petersen K. U., Reuss L. Cyclic AMP-induced chloride permeability in the apical membrane of Necturus gallbladder epithelium. J Gen Physiol. 1983 May;81(5):705–729. doi: 10.1085/jgp.81.5.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reuss L. Basolateral KCl co-transport in a NaCl-absorbing epithelium. Nature. 1983 Oct 20;305(5936):723–726. doi: 10.1038/305723a0. [DOI] [PubMed] [Google Scholar]
  21. Reuss L., Costantin J. L. Cl-/HCO3- exchange at the apical membrane of Necturus gallbladder. J Gen Physiol. 1984 Jun;83(6):801–818. doi: 10.1085/jgp.83.6.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reuss L., Finn A. L. Electrical properties of the cellular transepithelial pathway in Necturus gallbladder. I. Circuit analysis and steady-state effects of mucosal solution ionic substitutions. J Membr Biol. 1975 Dec 4;25(1-2):115–139. doi: 10.1007/BF01868571. [DOI] [PubMed] [Google Scholar]
  23. Reuss L., Finn A. L. Electrical properties of the cellular transepithelial pathway in Necturus gallbladder. II. Ionic permeability of the apical cell membrane. J Membr Biol. 1975 Dec 4;25(1-2):141–161. doi: 10.1007/BF01868572. [DOI] [PubMed] [Google Scholar]
  24. Reuss L. Independence of apical membrane Na+ and Cl- entry in Necturus gallbladder epithelium. J Gen Physiol. 1984 Sep;84(3):423–445. doi: 10.1085/jgp.84.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Reuss L., Reinach P., Weinman S. A., Grady T. P. Intracellular ion activities and Cl-transport mechanisms in bullfrog corneal epithelium. Am J Physiol. 1983 May;244(5):C336–C347. doi: 10.1152/ajpcell.1983.244.5.C336. [DOI] [PubMed] [Google Scholar]
  26. Spring K. R., Ericson A. C. Epithelial cell volume modulation and regulation. J Membr Biol. 1982;69(3):167–176. doi: 10.1007/BF01870396. [DOI] [PubMed] [Google Scholar]
  27. Weinman S. A., Reuss L. Na+-H+ exchange and Na+ entry across the apical membrane of Necturus gallbladder. J Gen Physiol. 1984 Jan;83(1):57–74. doi: 10.1085/jgp.83.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weinman S. A., Reuss L. Na+-H+ exchange at the apical membrane of Necturus gallbladder. Extracellular and intracellular pH studies. J Gen Physiol. 1982 Aug;80(2):299–321. doi: 10.1085/jgp.80.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]

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