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

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Abstract
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.