ESCHERICHIA-COLI HEAT-STABLE ENTEROTOXIN-MEDIATED COLONIC CL- SECRETION IS ABSENT IN CYSTIC-FIBROSIS

Background/Aims: Calcium- and adenosine 3',5'-cyclic monophosphate (cA MP)-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 Es cherichia coli heat-stable enterotoxin (STa) on rectal ion transport o f 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- tr ansport was also evaluated in 24-hour primary cultures of human colono cytes using 6-methoxy-quinolyl-acetoethyl ester in response to STa (1 mu mol/L) and 8 bromo-cGMP (100 mu mol/L) with or without Cl- transpor t inhibitors. Results: Whereas STa increased rectal potential differen ce in controls, there was no effect in cystic fibrosis subjects. STa s timulated the cGMP concentration in rectal biopsy specimens from both control and cystic fibrosis subjects approximately twofold. In vitro C l- transport in non-cystic fibrosis colonocytes increased threefold an d fivefold with STa and and 8-bromo-cGMP, respectively. These transpor t increases were inhibited by furosemide and the Cl- channel blocker d iphenylamine-2-carboxylate. Conclusions: Human colonocytes secrete Cl- in response to STa and cGMP in normal subjects, but this response is absent in cystic fibrosis.