Docosahexaenoic acid selectively augments muscarinic stimulation of epithelial Cl- secretion.
BACKGROUND
We investigated the effect of various fatty acids on electrogenic chloride secretion in T84 cells, a model for intestinal epithelium.


METHODS
T84 intestinal epithelial cells grown on permeable supports were studied by conventional current-voltage clamping. Membrane lipids from T84 cells were extracted, transmethylated, and analyzed by gas chromatography. Lipid extracts were fractionated into nonpolar, free fatty acids, and phospholipids by amynopropil column chromatography.


RESULTS
Docosahexaenoic acid (DHA) but not eicosapentanoic acid or other fatty acids selectively enhanced the secretory response to the muscarinic agonist carbachol but not the response to other Ca2+ agonists (histamine, thapsigargin, or ionomycin) or the response to the cAMP agonist forskolin. The ability of DHA to augment Cl- secretion appeared to correlate closer with free DHA levels than with membrane-bound DHA. Other effects of DHA on T84 cells included a reduction in transepithelial resistance (a measure of barrier function), actions that were dissociated from the effect on Cl- secretion.


CONCLUSIONS
The results suggest that DHA, which has been shown to reverse organ pathology in experimental cystic fibrosis, may selectively affect agonist-regulated transport events and other fundamental properties of epithelial cells.
Del Castillo
Isabel Calvo
IC
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Alvarez
Juan G
JG
Freedman
Steven D
SD
Ollero
Mario
M
Claros
Leonardo
L
Song
J Cecilia
JC
Yoo
James
J
Matthews
Jeffrey B
JB
D002217:Carbachol / Q000378:metabolism*; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008954:Models, Biological; D018721:Muscarinic Agonists / Q000378:metabolism*
D002712:Chlorides; D018721:Muscarinic Agonists; D004281:Docosahexaenoic Acids; D002217:Carbachol