Chloride secretion by canine tracheal epithelium: I. Role of intracellular c AMP levels.
We measured the short-circuit current (Isc) 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 decrease both Isc and cellular cAMP levels; (ii) PGF2 alpha and calcium ionophore, A23187, increase Isc without affecting cell cAMP levels at the doses employed; and (iii) acetylcholine, histamine, and phenylephrine do not alter either Isc 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 beta-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 of Isc 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 decreases Isc 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.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone; D004285:Dogs; D004848:Epithelium / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D011458:Prostaglandins E / Q000096:biosynthesis; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism*
D002712:Chlorides; D011458:Prostaglandins E; D011465:Prostaglandins, Synthetic; D013806:Theophylline; D000242:Cyclic AMP; D015232:Dinoprostone; D000109:Acetylcholine; D002118:Calcium; D007213:Indomethacin