STb enterotoxin of Escherichia coli: cyclic nucleotide-independent secretion.

Abstract

Escherichia coli may produce a heat-labile enterotoxin (LT) or two heat-stable enterotoxins (STa, STb). Experimentally, STb is consistently active only in 5 h-weaned pig intestinal loops (WPIL), an effect that is largely removable by rinsing. At least three mechanisms initiate small intestinal secretion: cyclic AMP (LT), cyclic GMP (STa) and calcium (A23187). All three increase short-circuit current (SCC) in Ussing chambers by stimulating net Cl- secretion. STb significantly increases SCC within 2-5 minutes in Ussing chambers and is independent of cyclic AMP and cyclic GMP. When compared to crude culture filtrates of a non-toxigenic strain of E. coli, crude culture filtrates of STb did not alter Na+ or Cl- undirectional or net fluxes. However, the calculated residual ion flux (JRnet) increased significantly in STb-treated tissues and appeared to largely account for the STb-induced increase in SCC. Furosemide applied serosally (10(-3) M), the removal of extracellular calcium, and lanthanum chloride (10(-3) M) did not inhibit the effect of STb on SCC. Chlorpromazine (0.4 mM) completely inhibited STb-induced secretion in porcine loops. This inhibition was a non-specific reversal of the STb effect because in Ussing chambers, chlorpromazine simply induced an equal and opposite effect on SCC. These results indicate that STb initiates intestinal secretion in porcine jejunum in vitro by stimulating primarily non-chloride anion secretion in the absence of extracellular calcium. We postulate that STb causes bicarbonate secretion by a mechanism distinct from those of previously studied enterotoxins.