Feb 1, 1963

An analysis of the direct and indirect actions of drugs on the isolated guinea-pig ileum

British Journal of Pharmacology and Chemotherapy


The responses of the isolated guinea-pig ileum to coaxial stimulation of its nerves, to histamine, acetylcholine, bradykinin, nicotine, tetramethylammonium, 1,1-dimethyl-4-phenyl-piperazinium iodide and 5-hydroxytryptamine were studied, before and during anoxia, cooling, or exposure to hyoscine, phenoxybenzamine hydrochloride, morphine or hexamethonium. Dose ratios were used to determine the amount of block induced by these procedures. With the response to coaxial nerve stimulation as an indication of the excitability of the nervous tissue, it was found that anoxia or cooling abolished the response to single shocks. Under these conditions the response of the ileum to histamine, acetylcholine and bradykinin was hardly affected, indicating a direct action of these substances on the muscle fibres. The effects of nicotine, tetramethylammonium, dimethylphenylpiperazinium and 5-hydroxytryptamine were reduced to various degrees, and we have concluded that their main actions are indirect, through stimulation of cholinergic nerve fibres. When these indirect actions were prevented, increasing the dose revealed a direct action, a larger increase in dose being required for 5-hydroxytryptamine and dimethylphenylpiperazinium than for tetrame...Continue Reading

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Mentioned in this Paper

Histamine Measurement
Cholinergic Nerves
Cold Temperature
Phenoxybenzamine Hydrochloride
Morphine Measurement

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