Effects of F-actin stabilization or disassembly on epithelial Cl- secretion and Na-K-2Cl cotransport.
Previous studies showed that cAMP-dependent transepithelial Cl- secretion of the intestinal cell line T84 is reduced by the F-actin stabilizer phalloidin, an effect in part attributable to inhibition of basolateral Na-K-2Cl cotransport. However, secretory responses are preserved in cells treated with the microfilament disrupter cytochalasin D. We explored the effects of cytochalasin D and two novel compounds derived from marine sponges on the Cl- secretory apparatus of T84 cells. Jasplakinolide (which stabilizes F-actin inhibited cAMP-dependent secretion and Na-K-2Cl cotransport. Latrunculin A (which sequesters G-actin monomers) profoundly altered the distribution of F-actin and reduced basal transepithelial resistance with minimal effect on secretion. Cytochalasin D, but not latrunculin A, activated Na-K-2Cl cotransport. The results provide further evidence that vectorial ion transport is influenced by the cytoskeleton and support a model in which disassembly of F-actin by specific pharmacological means or in response to secretory agonists favors activation of Na-K-2Cl cotransport.
Matthews
J B
JB
Department of Surgery, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Smith
J A
JA
Hrnjez
B J
BJ
D000199:Actins / Q000378:metabolism* / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000502:physiology; D047630:Depsipeptides; D004355:Drug Stability; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins; D002712:Chlorides; D047630:Depsipeptides; D010456:Peptides, Cyclic; D028021:Sodium-Potassium-Chloride Symporters; D013844:Thiazoles; D053778:Thiazolidines; C057531:jasplakinolide; D015638:Cytochalasin D; C037067:latrunculin A