The action of drugs on the circular muscle strip from the guinea-pig isolated ileum.

The circular muscle strip is a new preparation for examining the action of drugs on the circular muscle of the guinea-pig isolated intestine. The preparation differed from the longitudinal muscle in that it was insensitive to drugs which act on autonomic effector tissues but, after inhibition of cholinesterase, it responded readily to choline esters, 5-hydroxytryptamine, histamine and nicotine. This behaviour necessitated the treatment of each strip with the anticholinesterase NN-diisopropylphosphodiamidic fluoride (mipafox) before each experiment. The contractions of the strip by 5-hydroxytryptamine, histamine and nicotine were abolished by procaine, botulinum toxin (Type A), morphine and hemicholinium, whilst the actions of acetylcholine and methacholine were unaffected. Contractions of the strip in response to each of the drugs were abolished by atropine and hyoscine. The action of nicotine was specifically antagonized by hexamethonium, that of 5-hydroxytryptamine by desensitization of the tissue to 5-hydroxytryptamine, and that of histamine either by desensitization of the tissue to histamine or by mepyramine. It is postulated that 5-hydroxytryptamine, histamine and nicotine stimulate specific receptor sites within the intramural nerve plexuses of the guinea-pig isolated ileum. Finally, botulinum toxin (Type A), morphine or hemicholinum, acting on the neuronal elements of the intramural plexuses, depressed the contractions of the circular muscle strip due to histamine or nicotine more readily than those due to 5-hydroxytryptamine.