Role of prostaglandins and enteric nerves in Escherichia coli heat-stable enterotoxin (STa)-induced intestinal secretion in pigs

Objective - To examine the role of prostaglandins and enteric nerves in mediating intestinal secretion induced by enterotoxigenic Escherichia coli heat-stable enterotoxin (STa) in pig jejunum and distal portion of the colon Animals - Two- to 3-week-old suckling crossbred pigs were studied Design - Changes in ion transport in response to mucosal addition of E coli STa to jejunal and colonic tissues were studied in the presence and absence of inhibitors Procedure - Flat sheets of muscle-stripped proximal portions of the jejunum and distal portions of the colon were mounted in Ussing chambers equipped to measure changes in short-circuit current (lsc), a measure of active ion transport. Tissues were exposed to 200 ng of STa/ml administered to mucosal solutions, and subsequent changes in lsc were recorded. Results - In control tissues, changes in lsc induced by STa in the distal colon were significantly greater (21.4 ± 4 μA/cm²) than those observed in the jejunum (14.0 ± 2 μA/cm²). When either segment was exposed to the neurotoxin, tetrodotoxin, or to the nitric oxide synthase inhibitor, N^G-nitro-L-arginine-methyl ester, lsc responses to STa were unchanged, suggesting no involvement of sub-mucosal nerves in mediating STa-induced secretion. When tissues from the distal portion of the colon and jejunum were pretreated with piroxicam, a prostaglandin synthesis inhibitor, the STa-induced lsc response was significantly reduced by 52 and 57%, respectively. Conclusions - These results indicate that the pig jejunum and distal portion of the colon are sensitive to the secretory actions of enterotoxigenic E coli STa, and that the responses are mediated, in part, by release of prostaglandins.