The striped external muscle of the isolated guinea-pig oesophagus is insensitive to drugs and the lumen does not seem to be patent; thus the preparation does not respond to drugs until they have penetrated the external muscle and stimulated the intramural nerves or the plain muscle of the muscularis mucosae. The innervation of the external muscle of the guinea-pig oesophagus is not blocked by hexamethonium and is apparently without ganglia, so a stimulant of ganglion-cells produces a contraction of the muscularis mucosae only, which is distinguishable from a contraction of the external muscle. Furthermore, the external muscle and the muscularis mucosae can be separated, so that the actions of drugs on the muscularis mucosae in situ can be compared with those on the separated muscularis mucosae (Bartlet, 1968a, b). Hence the structure of the guinea-pig oesophagus makes it a suitable preparation for analysing the actions of drugs on the intramural nervous plexuses and muscularis mucosae of the alimentary tract, and a description of the actions of 5-hydroxytryptamine (5-HT) and histamine on this preparation follows.
METHODSPreparations of muscularis mucosae, external muscle, oesophagus and oesophagus with vagus nerve attached were made as before (Bartlet, 1968a). The term " oesophagus " in the text, tables and figures refers to the whole organ, and the terms " external muscle " and " muscularis mucosae " refer to the separated oesophageal layers. The preparations were exposed to agonists for 1-3 min in every 15 min. Antagonists were added to the Krebs solution bathing the preparation when reproducible responses to an agonist had been obtained, only one agonist being tested in any such experiment with an antagonist. The effect of antagonists was expressed in terms of the dose ratio (Gaddum, Hameed, Hathway & Stephens, 1955), which is the ratio of equi-active doses of agonist in the presence and absence of antagonist. The inverse ratio was used to express the effect of drugs which potentiated agonists.The following drugs were used: acetylcholine chloride, acetyl-/3-methylcholine chloride, atropine sulphate, carbachol chloride, cocaine hydrochloride, eserine salicylate, hexamethonium bromide, histamine acid phosphate, 5-hydroxytryptamine creatinine sulphate, hyoscine hydrobromide, mepyramine maleate, methysergide bimaleate, muscarine iodide and tubocurarine chloride. The muscarine iodide was kindly supplied by J. R. Geigy & Co., Basel, Switzerland. Quantities of the drugs in the text, tables and figures refer to the above salts.