Effect of Pseudomonas aeruginosa exotoxin-A on the synthesis and secretion of proteins in isolated rat pancreatic acini.

Exposure of isolated rat dispersed pancreatic acini to increasing concentrations (10 to 1000 ng/ml) of purified exotoxin-A from Pseudomonas aeruginosa resulted in a progressive inhibition of 3H-leucine incorporation into "cellular" (those remaining in the cells) and "secretory" (those released into the medium) proteins. With each concentration of exotoxin-A, magnitude of reduction was found to be greater for the "secretory" proteins than that observed for the "cellular" proteins. Thus, in the presence of 250 ng/ml of exotoxin-A, a dose that produced maximal inhibition in protein synthesis, 3H-leucine incorporation into "cellular" and "secretory" proteins was found to be decreased by about 19 and 50%, respectively, when compared with the corresponding basal controls. Release of trypsinogen, chymotrypsinogen and amylase from the isolated pancreatic acini was also inhibited by high doses of exotoxin-A. However, whereas the exotoxin concentration of 1000 ng/ml, caused a near complete inhibition of chymotrypsinogen release, trypsinogen and amylase secretion were decreased by 40 and 50%, respectively. It is concluded that in isolated pancreatic acini, exotoxin-A inhibits the synthesis and secretion of proteins.