Activation of intestinal Na-K-2Cl cotransport by 5'-AMP requires F-actin remodeling.
BACKGROUND
Although cyclic adenosine monophosphate (cAMP)-dependent intestinal chloride ion (Cl-) secretion is regulated primarily at the level of apical Cl- channels, cAMP also elicits basolateral microfilament remodeling and activates basolateral sodium-potassium-2 chloride (Na-K-2Cl) cotransport. Without these additional events, secretion is inhibited. However, it is unclear whether microfilament-dependent activation of Na-K-2Cl cotransport is a direct effect of cAMP or a secondary response to the opening of apical Cl- channels.


METHODS
Using the human intestinal epithelial cell line T84, we examined Cl- secretion elicited by 5'-adenosine monophosphate (5'-AMP), a novel agonist that activates apical Cl- channels without elevation of intracellular cAMP.


RESULTS
5'-AMP was found to activate basolateral Na-K-2Cl cotransport, but such regulation was abolished by the actin stabilizer, phalloidin.


CONCLUSIONS
Basolateral Na-K-2Cl cotransport appears to be regulated, at least in part, as an indirect response to activation of apical Cl- channels, a pathway of regulation which may require cytoskeletal remodeling.
Matthews
J B
JB
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts 02215.
Tally
K J
KJ
Smith
J A
JA
D000199:Actins / Q000502:physiology*; D000249:Adenosine Monophosphate / Q000494:pharmacology* / Q000502:physiology; D002460:Cell Line; D002713:Chlorine / Q000378:metabolism*; D000242:Cyclic AMP / Q000819:agonists / Q000502:physiology*; D004594:Electrophysiology; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D010590:Phalloidine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D012414:Rubidium Radioisotopes / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012964:Sodium / Q000378:metabolism*
D000199:Actins; D012414:Rubidium Radioisotopes; D010590:Phalloidine; D000249:Adenosine Monophosphate; D002713:Chlorine; D012964:Sodium; D000242:Cyclic AMP; D011188:Potassium