Clostridium difficile toxin A stimulates enzyme secretion from isolated rat pancreatic acini

Although Cl difficile bacteremia and the presence of antibodies to toxin A (TxA) have been reported, little information is available at present on TxA effect on the functional properties of various visceral organs. We have, therefore, examined the in vitro effects of TxA on amylase and trypsin secretion from rat isolated pancreatic acini. Dispersed rat pancreatic acini were exposed for 60 min to different concentrations of highly purified TxA and the rate of amylase, trypsin and LDH release were monitored. Free cytosolic calcium release in pancreatic acini after toxin A (10(-10)M to 10(-8)M) treatment was measured with Fura-2/AM, Ca-indicator dye. TxA (10(-10) to 10(-8)M) increased significantly the rate of both the amylase and trypsin secretion without any membrane damage, with toxin A exerting its action via calcium dependent pathway as suggested by intracellular calcium release measured with Fura-2/AM.