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Published on: August 19, 2016
Some pharmacological properties of the alpha-toxin of staphylococcus pyogenes
Abstract:
The alpha-toxin of Staphylococcus pyogenes produced a slowly developing contracture of isolated preparations of rabbit jejunum and of guinea-pig ileum which persisted after thorough washing and left the gut unresponsive to further doses of alpha-toxin or of acetylcholine. After incubation with antitoxin, the alpha-toxin no longer produced a contracture. Antitoxin only prevented the alpha-toxin response if added to the bath fluid before but not after the alpha-toxin. Certain drugs reduced the alpha-toxin contracture when added to the bath fluid before or after the alpha-toxin, but the contracture reappeared on washing. Papaverine abolished the contracture and pethidine was only slightly less active. Mepyramine, amyl nitrite, caffeine, aminophylline, adrenaline and ephedrine partly reduced the contracture. Hexamethonium, cocaine, tubocurarine and gallamine had no effect. The effect of atropine was only small. The gut-stimulant activity/haemolytic unit of two alpha-toxin samples differed greatly; this difference did not appear to be due to activity of impurities. The implications of these observations are discussed.
Insights
Staphylococcus pyogenes alpha-toxin causes persistent gut contracture, blocked by antitoxin. Several drugs, notably papaverine and pethidine, can reduce or abolish this effect.
Area of Science:
- Microbiology
- Pharmacology
- Gastroenterology
Background:
- Staphylococcus pyogenes alpha-toxin is a potent exotoxin.
- The physiological effects of alpha-toxin on gastrointestinal smooth muscle are not fully understood.
Purpose of the Study:
- To investigate the effects of Staphylococcus pyogenes alpha-toxin on isolated rabbit jejunum and guinea-pig ileum.
- To determine the efficacy of antitoxin and various pharmacological agents in modulating the alpha-toxin-induced contracture.
Main Methods:
- Isolated rabbit jejunum and guinea-pig ileum preparations were exposed to alpha-toxin.
- The effects of antitoxin and various drugs (papaverine, pethidine, mepyramine, etc.) on alpha-toxin-induced contracture were assessed.
- Gut-stimulant activity and haemolytic units of alpha-toxin samples were compared.
Main Results:
- Alpha-toxin induced a persistent, irreversible contracture of isolated gut preparations.
- Antitoxin prevented the contracture if added before, but not after, alpha-toxin.
- Papaverine and pethidine were highly effective in abolishing or reducing the contracture, while other agents showed varying degrees of efficacy.
Conclusions:
- Staphylococcus pyogenes alpha-toxin elicits a sustained contractile response in the gut, potentially through mechanisms not immediately neutralized by antitoxin.
- Pharmacological agents like papaverine and pethidine demonstrate significant potential in mitigating the effects of alpha-toxin on gastrointestinal motility.
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