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In Vitro Characterization of the Electrophysiological Properties of Colonic Afferent Fibers in Rats
Published on: September 27, 2017
Effect of alpha-2 adrenoceptor antagonists on colonic function in rats
O Yamamoto1, H Niida, K Tajima
1Discovery Research Laboratories, Nippon Shinyaku Co. Ltd., Nishiohji-Hachijo, Minami-ku, Kyoto, Japan. o.yamamoto@po.nippon-shinyaku.co.jp
Abstract:
We studied the effect of alpha-2 adrenoceptor antagonists on colonic function stimulated by water-avoidance stress, 5-hydroxytryptamine (5-HT), bethanechol and castor oil by comparison with the effects of atropine and a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, ondansetron. Yohimbine, idazoxan and atropine, but not ondansetron, significantly inhibited water-avoidance stress-stimulated faecal excretion. Yohimbine and idazoxan inhibited neither 5-HT- nor bethanechol-stimulated faecal excretion. In contrast, atropine inhibited both 5-HT- and bethanechol-stimulated faecal excretion and ondansetron inhibited 5-HT-stimulated faecal excretion. Yohimbine did not inhibit the incidence of diarrhoea induced by castor oil, but idazoxan significantly inhibited diarrhoea observed during a 1-h period after the administration of castor oil. Both atropine and ondansetron inhibited diarrhoea during a 2-h period after the administration of castor oil. These findings suggest that alpha-2 adrenoceptor antagonists specifically inhibit colonic motor function stimulated by stress in rats.
Insights
Alpha-2 adrenoceptor antagonists specifically reduce stress-induced colonic motor function in rats. These antagonists, like yohimbine and idazoxan, show targeted effects on stress-related fecal excretion, unlike other tested agents.
Area of Science:
- Pharmacology
- Gastroenterology
- Neuroscience
Background:
- Colonic function is modulated by various neurotransmitters and stress.
- Alpha-2 adrenoceptors play a role in regulating gastrointestinal motility.
- Understanding the specific mechanisms of stress-induced colonic dysfunction is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the effects of alpha-2 adrenoceptor antagonists on stress-induced colonic function.
- To compare the efficacy of alpha-2 adrenoceptor antagonists with other agents like atropine and ondansetron in modulating colonic responses.
- To determine the specificity of alpha-2 adrenoceptor antagonists in inhibiting stress-related colonic motor activity.
Main Methods:
- Administration of alpha-2 adrenoceptor antagonists (yohimbine, idazoxan) and control drugs (atropine, ondansetron) to rats.
- Stimulation of colonic function using water-avoidance stress, 5-hydroxytryptamine (5-HT), bethanechol, and castor oil.
- Measurement of faecal excretion and incidence of diarrhoea as indicators of colonic motor function.
Main Results:
- Yohimbine, idazoxan, and atropine significantly inhibited water-avoidance stress-stimulated faecal excretion; ondansetron did not.
- Alpha-2 antagonists did not inhibit 5-HT- or bethanechol-stimulated faecal excretion, whereas atropine did.
- Idazoxan, but not yohimbine, significantly inhibited castor oil-induced diarrhoea, while atropine and ondansetron inhibited diarrhoea over a 2-h period.
Conclusions:
- Alpha-2 adrenoceptor antagonists selectively inhibit stress-induced colonic motor function in rats.
- These findings highlight the specific role of alpha-2 adrenoceptors in mediating the colonic response to stress.
- Alpha-2 adrenoceptor antagonists represent a potential therapeutic target for stress-related gastrointestinal disorders.
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