title: Adenosine scavenging: a novel mechanism of chloride secretory control in intestinal epithelial cells.
abstract: BACKGROUND
  Adenosine released by cells during ischemia typically serves as a feedback inhibitor of further organ work. However, in ischemic intestine, adenosine appears to act via stimulatory A2b receptors to increase work in the form of chloride ion (Cl-) secretion. This unusual response may contribute to luminal fluid sequestration in intestinal ischemia. In nonischemic cells feed-forward activation of Cl- secretion does not occur despite the fact that adenosine may be continuously generated during normal cell metabolism. Thus we postulated that intestinal epithelia normally control the disposition of adenosine to prevent inappropriate activation of secretion.
  
  
  METHODS
  Model T84 intestinal epithelia were studied by means of electrophysiologic and isotopic techniques.
  
  
  RESULTS
  Dipyridamole and nitrobenzylthioinosine (inhibitors of nucleoside transport) and iodotubercidin (an inhibitor of adenosine kinase) caused adenosine to accumulate extracellularly and induced a Cl- secretory response that was prevented by adenosine receptor blockade. Uptake of exogenous adenosine was restricted to the basolateral compartment and was blocked by nucleoside transport inhibitors.
  
  
  CONCLUSIONS
  Adenosine released from nonischemic intestinal epithelial cells is scavenged by a basolaterally restricted adenosine transporter. This system maintains extracellular adenosine levels below the prosecretory threshold and thus limits adenosine-elicited activation of Cl- secretion (and hence diarrhea) under normal conditions).
authors: Department of Surgery, Beth Israel Hospital, Boston, Mass. 02215, USA.
authors: K J
authors: KJ
authors: Tally
authors: B J
authors: BJ
authors: Hrnjez
authors: J A
authors: JA
authors: Smith
authors: E C
authors: EC
authors: Mun
authors: J B
authors: JB
authors: Matthews
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002021:Buffers; D002478:Cells, Cultured / Q000201:enzymology / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009705:Nucleosides / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002021:Buffers; D002712:Chlorides; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009705:Nucleosides; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; C034214:5-iodotubercidin; D004176:Dipyridamole; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000248:Adenosine Kinase; D000241:Adenosine; D014372:Tubercidin