Pseudomonas aeruginosa cytotoxin stimulates secretion of amylase and protease zymogens with a concomitant decrease of mRNA levels in isolated rat pancreatic acini

The action of Pseudomonas aeruginosa cytotoxin on isolated pancreatic acini was investigated. The release of amylase and serine protease zymogens from the isolated rat pancreatic acini was induced with increasing amounts of cytotoxin in vitro. The stimulated release of amylase reached 30% of total cellular content with 100 micrograms/mL of the purified cytotoxin. The induced release of amylase, trypsinogen, proelastase, and chymotrypsinogen reached the maximum after 75 minutes of incubation while lactate dehydrogenase began to appear after 15 minutes of incubation with a secondary biphasic increase at 75 min of incubation. The concentrations of acinar mRNAs of amylase, trypsinogen, proelastase, and chymotrypsinogen, as measured by dot-blot hybridization with the cloned cDNAs of amylase, trypsinogen I, proelastase II, and chymotrypsinogen B of the rat, decreased with time and were significantly lower than in the untreated acini. It is concluded that cytotoxin stimulates the release of amylase and protease zymogens with a concomitant increase in membrane permeability and a decrease of cellular mRNA levels. The inhibition of gene expression is attributable merely to a generalized toxic effect upon cellular metabolism.