Mucosal adenosine stimulates chloride secretion in canine tracheal epithelium.
Adenosine is a local regulator of a variety of physiological functions in many tissues and has been observed to stimulate secretion in several Cl-secreting epithelia. In canine tracheal epithelium we found that adenosine stimulates Cl secretion from both the mucosal and submucosal surfaces. Addition of adenosine, or its analogue 2-chloroadenosine, to the mucosal surface potently stimulated Cl secretion with no effect on the rate of Na absorption. Stimulation resulted from an interaction of adenosine with adenosine receptors, because it was blocked by the adenosine receptor blocker, 8-phenyltheophylline. The adenosine receptor was a stimulatory receptor as judged by the rank-order potency of adenosine and its analogues and by the increase in cellular adenosine 3',5'-cyclic monophosphate levels produced by 2-chloroadenosine. Adenosine also stimulated Cl secretion when it was added to the submucosal surface, although the maximal increase in secretion was less and it was much less potent. Part, but not all, of the lower potency of submucosal adenosine resulted from submucosal uptake and metabolism of the drug. The observation that mucosal 8-phenyltheophylline blocked the effect of submucosal 2-chloroadenosine, whereas submucosal 8-phenyltheophylline did not prevent a response to mucosal or submucosal 2-chloroadenosine, suggests that adenosine receptors are located on the mucosal surface. Thus submucosal adenosine may stimulate secretion by crossing the epithelium and interacting with receptors located on the mucosal surface. Because adenosine can be released from mast cells located in the airway lumen in response to inhaled material, and because adenosine stimulated secretion from the mucosal surface, it may be in a unique position to control the epithelium on a regional level.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009092:Mucous Membrane / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D011983:Receptors, Purinergic; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism*
D002712:Chlorides; D007473:Ion Channels; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D012964:Sodium; D013806:Theophylline; D000242:Cyclic AMP; C028322:8-phenyltheophylline; D000241:Adenosine