Beta-adrenergic blocking activity of Yersinia pestis murine toxin.
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.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D008053:Lipid Mobilization / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013696:Temperature; D015010:Yersinia pestis
D001427:Bacterial Toxins; D005230:Fatty Acids, Nonesterified; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D003994:Bucladesine; D005934:Glucagon; D002772:Cholera Toxin; D000262:Adenylyl Cyclases; D004837:Epinephrine