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Beta-adrenergic blocking activity of Yersinia pestis murine toxin
Abstract:
Yersinia pestis plague murine toxin has been found to inhibit the mobilization of free fatty acids in mice in a manner similar to that of beta-adrenergic blocking agents. The blockage is detectable 75 min after injection of the toxin (1 to 2 mean lethal doses). The degree of inhibition was directly correlated with the toxicity of a given toxin preparation. Agents such as cholera toxin or glucagon, with apparently distinct receptors from beta-adrenergic receptors, stimulated adenylate cyclase and lipolysis and effectively modified toxicity. Likewise, cyclic adenosine 3',5'-monophosphate bypassed the toxin block and antagonized toxicity. Energy-rich compounds such as fatty acids, organic acids, and glucose effectively modified the intoxication process. The biological activity of plague toxin showed profound temperature sensitivity. Mice placed at 5 degrees C were highly susceptible to the effects of the toxin, whereas mice placed at 37 degrees C were totally resistant to intoxication. Results showed that plague toxin cannot block epinephrine-induced mobilization of free fatty acids in mice placed at 37 degrees C. These studies suggested that plague toxin acts at the receptor level in a manner similar to that of beta-adrenergic blocking agents. A complete, analogous activity was shown between toxin and known beta-adrenergic antagonists in their effect on beta-adrenergic agonist action in stimulating lipolysis. It is hypothesized that, since toxin shows no in vitro activity, it is in some way modified in animals.
Insights
Yersinia pestis plague toxin inhibits free fatty acid mobilization in mice, acting similarly to beta-adrenergic blockers. Temperature and energy-rich compounds significantly affect toxin toxicity and its mechanism.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Yersinia pestis plague toxin interferes with free fatty acid (FFA) mobilization in mice.
- This inhibition resembles the action of beta-adrenergic blocking agents.
Purpose of the Study:
- To investigate the mechanism of action of Yersinia pestis plague toxin.
- To explore the relationship between plague toxin and beta-adrenergic signaling pathways.
- To identify factors influencing plague toxin toxicity.
Main Methods:
- Administered Yersinia pestis plague toxin to mice at varying temperatures.
- Assessed FFA mobilization and lipolysis.
- Investigated the effects of cholera toxin, glucagon, cyclic adenosine 3',5'-monophosphate, and energy-rich compounds.
Main Results:
- Plague toxin inhibited FFA mobilization in a dose-dependent manner, correlating with toxicity.
- Cholera toxin and glucagon modulated toxicity, while cyclic adenosine 3',5'-monophosphate antagonized it.
- Temperature significantly impacted toxin activity: mice at 5°C were susceptible, while those at 37°C were resistant.
- Plague toxin did not block epinephrine-induced FFA mobilization at 37°C.
Conclusions:
- Yersinia pestis plague toxin likely acts at the receptor level, mimicking beta-adrenergic blocking agents.
- The toxin's activity is temperature-dependent and can be modified by various biological and chemical agents.
- In vivo modification of the toxin is suggested due to lack of in vitro activity.