Stimulation of faecal excretion in rats by α2-adrenergic antagonists

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Abstract
The effects of several α-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 α2-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 α1-antagonist with putative affinity for the α2B-receptor subtype, was the least effective (AD1 > 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 α2-adrenergic receptors, whose blockage by specific antagonists induces faecal excretion. The α2A-receptor subtype appears to be the most likely candidate for controlling faecal excretion through inhibition of acetylcholine release.