Dynamic role of microfilaments in intestinal chloride secretion.
The importance of microfilaments in the regulation of chloride (Cl-) secretion by the human intestinal cell line T84 was investigated using the cytoskeletal probe phalloidin to bind and stabilize F-actin. Phalloidin was found to inhibit secretion mediated by cyclic adenosine monophosphate (cAMP) and the sustained secretory response to the calcium (Ca+2) ionophore ionomycin but not to affect the transient Ca+2-mediated response to carbachol and histamine. Fluorescent microscopic examination of F-actin revealed regionally restricted microfilament remodeling in cAMP- and ionomycin-treated cells. Normal regulation of apical Cl- and basolateral potassium (K+) channel functions was evident in phalloidin-loaded cells. It is concluded that prevention of cytoskeletal remodeling by actin stabilization inhibits the generation of a sustained Cl- secretory response by a mechanism that does not involve Cl- or K+ channels. Depolymerization of F-actin plays an integral role in the regulation of intestinal Cl- secretion.
Matthews
J B
JB
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts 02215.
Awtrey
C S
CS
Tally
K J
KJ
Smith
J A
JA
D008841:Actin Cytoskeleton / Q000502:physiology*; D000199:Actins / Q000187:drug effects* / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D017136:Ion Transport / Q000502:physiology; D015759:Ionomycin / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D010590:Phalloidine / Q000494:pharmacology*
D000199:Actins; D002712:Chlorides; D010590:Phalloidine; D015759:Ionomycin; D006632:Histamine; D002217:Carbachol; D000242:Cyclic AMP