Action of 5-hydroxytryptamine on the human stomach, duodenum, and jejunum in vitro.

EDITORIAL SYNOPSIS These pharmacological studies on human alimentary smooth muscle show that different regions of gut respond differently. Where a response is obtained it is due to a direct action on the muscle. It is generally accepted that alimentary smooth muscle contracts in the presence of 5-hydroxy-tryptamine (5-HT). This appears to be true for several animal species. Erspamer (1940, 1952) showed that rat duodenum and mouse jejunum were sensitive to small concentrations of this amine. Later Gaddum (1953) and Gaddum and Hameed (1954) reported that rat duodenum and colon, rabbit duodenum and jejunum, and guinea-pig duodenum, jejunum, and ileum all contracted in the presence of 5-HT and Gaddum described specific receptors for this amine. The fundus of the rat stomach was found to be a useful preparation for the assay of 5-HT, the longitudinal muscle being more sensitive than the circular (Vane, 1957). It is also well known that the human alimentary tract is sensitive to 5-HT, but most investigators have confined their attention to the effects of this amine on the motility and intraluminal pressure of the jejunum and ileum. Hendrix, Atkinson, Clifton, and Ingelfinger (1957) showed that intravenously administered 5-HT abruptly increased the intra-luminal pressure of the human jejunum. This effect was inhibited by atropine but unaltered by hexa-methonium, and it was suggested that 5-HT acted on the cholinergic nerves distal to the ganglionic synapse. Haverback and Davidson (1958) also demonstrated that 5-HT increased jejunal activity in the normal human subject. This action was inhibited by the oral administration of 2-bromo-lysergic acid diethylamide but not by atropine. Daniel, Honour, and Bogoch (1960) reported that intravenously administered 5-HT produced an initial spasm of the human ileum which was followed by rhythmic contractions lasting several minutes. Antagonism was not achieved with atropine, morphine, nalorphine, or promethazine. However, 2-bromolysergic acid did antagonise the effect. They concluded that intravenously administered 5-HT acted directly on the muscle of the ileum. Recently, the human ileum and colon have been investigated using a standard pharmacological technique in vitro (Fishlock and Parks, 1963a; Fishlock, 1964). The terminal ileum was found to contract in the presence of a small concentration of 5-HT. The ascending colon was comparatively insensitive and variable in response, but the whole of the distal half of the colon was very sensitive and regularly relaxed. This remarkable difference between the ileum and the colon prompted us to investigate other regions of the human intestinal …