Stimulation of enzyme secretion from isolated pancreatic acini by Clostridium difficile toxin B.
Exposure of isolated rat pancreatic acini to increasing concentrations (10 ng - 800 ng/ml) of toxin B from Clostridium difficile produced a biphasic effect on the rate of secretion of amylase, trypsinogen, and chymotrypsinogen. Whereas doses of toxin B from 10-30 ng/ml increased enzyme secretion by 15-20%, doses between 30 ng and 60 ng/ml showed a regression of this effect, whereafter the rate of secretion of amylase, trypsinogen, and chymotrypsinogen increased with increasing concentrations of the toxin. Toxin B concentration of 800 ng/ml enhanced amylase, trypsinogen and chymotrypsinogen secretion by 119%, 185% and 195%, respectively, when compared with the basal level. Stimulation of enzyme secretion by toxin B was not affected by the presence of either actinomycin-D or cycloheximide, at a concentration which inhibited acinar RNA or protein synthesis by 80-90%. Although toxin B as well as CCK8, carbachol and secretin by themselves caused significant stimulation in amylase, trypsinogen and chymotrypsinogen secretion from isolated pancreatic acini, toxin B together with either CCK8, carbachol or secretin produced no further augmentation in enzyme secretion than what was observed with the secretagogues alone. It is concluded that toxin B of Cl. difficile exerts a direct effect on pancreatic acinar cells as evidenced by stimulation of enzyme secretion.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000633:toxicity*; D002217:Carbachol / Q000494:pharmacology; D002918:Chymotrypsin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012633:Secretin / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D014362:Trypsinogen / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; C031815:toxB protein, Clostridium difficile; D012633:Secretin; D002217:Carbachol; D014362:Trypsinogen; D000681:Amylases; D002918:Chymotrypsin; D012844:Sincalide