Phage shock proteins B and C prevent lethal cytoplasmic membrane permeability in Yersinia enterocolitica.

The bacterial phage shock protein (Psp) stress response system is activated by events affecting the cytoplasmic membrane. In response, Psp protein levels increase, including PspA, which has been implicated as the master effector of stress tolerance. Yersinia enterocolitica and related bacteria with a defective Psp system are highly sensitive to the mislocalization of pore-forming secretin proteins. However, why secretins are toxic to psp null strains, whereas some other Psp inducers are not, has not been explained. Furthermore, previous work has led to the confounding and disputable suggestion that PspA is not involved in mitigating secretin toxicity. Here we have established a correlation between the amount of secretin toxicity in a psp null strain and the extent of cytoplasmic membrane permeability to large molecules. This leads to a morphological change resembling cells undergoing plasmolysis. Furthermore, using novel strains with dis-regulated Psp proteins has allowed us to obtain unequivocal evidence that PspA is not required for secretin-stress tolerance. Together, our data suggest that the mechanism by which secretin multimers kill psp null cells is by causing a profound defect in the cytoplasmic membrane permeability barrier. This allows lethal molecular exchange with the environment, which the PspB and PspC proteins can prevent.

Pancreatic carcinogenesis: effect of secretin in the hamster- nitrosamine model.

The effect of exogenous secretin on pancreatic carcinogenesis in WO strain hamsters has been examined in the nitrosamine-ductular adenocarcinoma model. Secretin, 20 clinical U/kg, stimulated a maximal secretory response of pancreatic juice and bicarbonate when given iv. The same dose given sc for 6 weeks had no significant effect on pancreatic wet weight and DNA or RNA contents. However, when given to animals receiving N-nitrosobis(2-oxopropyl)amine [(BOP) CAS: 60599-38-4] (5 mg/kg), it reduced the latency and increased the induction rate of tumor development when compared with the carcinogen given alone to animals (secretin + BOP, 15 of 17 animals with tumors; BOP alone, 4 of 13 with tumors at 15 wk; P less than .002). These effects are consistent with secretin acting as a cocarcinogen in this model of pancreatic carcinogenesis.

[An experimental study of suikrepan]. / Eksperimental'noe izuchenie suikrepana.

Acute, subacute, and chronic experiments were performed to examine the toxicity, specific action, analgetic, and physicochemical properties of suicrepan derived from the porcine duodenal mucosa and the hormone secretin contained in it. Suicrepan was found to be an effective pancreatic extrasecretory function stimulant, by showing therapeutical benefits in experimental pancreatitis and analgesic effects. The drug was demonstrated to display a low toxicity.

Effect of chronically-administered secretin on the nude mouse.

Secretin plays an important role in the growth regulation of certain cancers in vitro. The nude mouse is a suitable model for evaluation of the effects of this hormone on tumor xenografts in vivo, but little is known about long-term actions of secretin in this species. We investigated the impact of chronically administered synthetic porcine secretin in the nude mouse. Six groups of mice (eight animals each) received twice-daily intraperitoneal injections of saline or secretin at 0.5, 5, 50, 500, or 5,000 micrograms/kg for 14 days. Body weight and general health were unaffected by exogenous secretin, and no apparent behavioral effects were observed. Seven abdominal organs were examined at necropsy and all were histologically normal. The only organ that showed a weight change was the pancreas (13% decrease at the highest secretin dose). This was accompanied by decreases in DNA and RNA content, indicating pancreatic hypoplasia. Secretin administration caused changes in DNA and/or RNA content (but not protein content or weight) in liver, small bowel, cecum, and large bowel. No effect of secretin on stomach or kidney was observed. Our work demonstrates the safety of frequent injections of pharmacologic doses of secretin in this frail animal and suggests that the nude mouse is an appropriate model for the in vivo study of tumor growth regulation by secretin.