Escherichia coli heat-stable enterotoxin-mediated colonic Cl- secretion is absent in cystic fibrosis.
OBJECTIVE
Calcium- and adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl- secretions in the human colon are abnormal in cystic fibrosis, but the effect of guanosine 3',5'-cyclic monophosphate (cGMP) is unknown. This study examined the effects of the cGMP activator Escherichia coli heat-stable enterotoxin (STa) on rectal ion transport of controls and subjects with cystic fibrosis.


METHODS
In vivo rectal potential difference (PD) was measured in response to 10(-7) mol/L STa in adult cystic fibrosis (n = 6) and control subjects (n = 7). Cl- transport was also evaluated in 24-hour primary cultures of human colonocytes using 6-methoxy-quinolyl-acetoethyl ester in response to STa (1 mumol/L) and 8-bromo-cGMP (100 mumol/L) with or without Cl- transport inhibitors.


RESULTS
Whereas STa increased rectal potential difference in controls, there was no effect in cystic fibrosis subjects. STa stimulated the cGMP concentration in rectal biopsy specimens from both control and cystic fibrosis subjects approximately twofold. In vitro Cl- transport in non-cystic fibrosis colonocytes increased threefold and fivefold with STa and 8-bromo-cGMP, respectively. These transport increases were inhibited by furosemide and the Cl- channel blocker diphenylamine-2-carboxylate.


CONCLUSIONS
Human colonocytes secrete Cl- in response to STa and cGMP in normal subjects, but this response is absent in cystic fibrosis.
Goldstein
J L
JL
Department of Medicine, University of Illinois at Chicago.
Sahi
J
J
Bhuva
M
M
Layden
T J
TJ
Rao
M C
MC
D000328:Adult; D001427:Bacterial Toxins / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002469:Cell Separation; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D006152:Cyclic GMP / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000503:physiopathology; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D008297:Male; D012007:Rectum / Q000473:pathology / Q000503:physiopathology; D012016:Reference Values
D001427:Bacterial Toxins; D002712:Chlorides; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C034151:heat stable toxin (E coli); D006152:Cyclic GMP