Stimulation of faecal excretion in rats by α2-adrenergic antagonists

The effects of several alpha-adrenoceptor antagonists on faecal output and water content in rats were investigated. Fed rats were treated either subcutaneously (s.c.) or orally with phentolamine, idazoxan, yohimbine, 1-(2-pyrimidinyl) piperazine (PmP) or prazosin. Drug potencies were compared on the basis of the dose inducing excretion of 1 g dry weight of faeces (AD1) by rats that do not normally excrete any faecal pellet during the observation time. The alpha 2-antagonist, idazoxan (AD1 = 0.25 mg kg-1, s.c.) was approximately 2.5, 4 and 8 times more potent than PmP, phentolamine and yohimbine in promoting faecal excretion. Prazosin, an alpha 1-antagonist with putative affinity for the alpha 2B-receptor subtype, was the least effective (AD1 greater than 5 mg kg-1, s.c.). The same compounds also increased the water content of faeces and had similar potencies by the oral route. Both clonidine (0.15 mg kg-1, s.c.) and atropine (0.2 mg kg-1, s.c.) significantly prevented the effects of all antagonists on faecal excretion. The present results are consistent with the view that rat colon is under tonic inhibitory control of prejunctional alpha 2-adrenergic receptors, whose blockage by specific antagonists induces faecal excretion. The alpha 2A-receptor subtype appears to be the most likely candidate for controlling faecal excretion through inhibition of acetylcholine release.