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Chloride secretion by canine tracheal epithelium: I. Role of intracellular cAMP levels

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Summary

We measured the short-circuit current (I sc) across canine tracheal epithelium and the intracellular cAMP levels of the surface epithelial cells in the same tissues to assess the role of cAMP as a mediator of electrogenic Cl secretion. Secretogogues fall into three classes: (i) epinephrine, prostaglandin (PG) E1, and theophylline increase bothI sc and cellular cAMP levels; (ii) PGF2α and calcium ionophore A23187, increaseI sc without affecting cell cAMP levels at the doses employed; and (iii) acetylcholine, histamine, and phenylephrine do not alter eitherI sc or cAMP levels.

These findings indicate that: (i) increases in cAMP or Ca activity stimulate electrogenic Cl secretion by the columnar cells of the surface epithelium; (ii) cAMP mediates the effects of PGE1 and β-adrenergic agonists; (iii) a strict correlation between cAMP levels and Cl secretion rate is not apparent from spontaneous variations in these parameters or from dose-response relations ofI sc and cAMP to epinephrine concentration; and (iv) acetylcholine, histamine, and phenylephrine, agents that stimulate electrically-neutral NaCl secretion by submucosal glands, do not evoke cAMP-mediated, responses by the surface epithelium.

Addition of 10−6 m indomethacin (or other prostaglandin synthesis inhibitors) to the mucosal solution decreasesI sc and cellular cAMP levels and reduces the release of PGE2 into the bathing media by 80%. Indomethacin does not interfere with the subsequent secretory response to PGE1. This suggests that endogenous prostaglandin production underlies the spontaneous secretion of Cl across canine tracheal epithelium under basal conditions.

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Author notes

  1. Philip L. Smith

    Present address: Department of Physiology, University of Kansas Medical Center, College of Health Sciences and Hospital Rainbow Boulevard at 39th, 66103, Kansas City, Kansas

  2. Michael J. Welsh

    Present address: Laboratory of Epithelial Transport and Kidney Physiology, Department of Internal Medicine, University of Iowa Hospitals, 52242, Iowa City, Iowa

  3. Raymond A. Frizzell

    Present address: Department of Physiology and Biophysics, University of Alabama in Birmingham, University Station, 35294, Birmingham, Alabama

Authors and Affiliations

  1. Department of Physiology and Cell Biology, University of Texas Medical School at Houston, 77025, Houston, Texas

    Philip L. Smith, Michael J. Welsh, Jeffrey S. Stoff & Raymond A. Frizzell

  2. Charles A. Dana Research Institute, The Harvard-Thorndike Laboratory and Department of Medicine, Beth Israel Hospital, 02215, Boston, Massachusetts

    Philip L. Smith, Michael J. Welsh, Jeffrey S. Stoff & Raymond A. Frizzell

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Smith, P.L., Welsh, M.J., Stoff, J.S. et al. Chloride secretion by canine tracheal epithelium: I. Role of intracellular cAMP levels. J. Membrain Biol. 70, 217–226 (1982). https://doi.org/10.1007/BF01870564

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