![]() ![]() However, when applied alone the antagonist raised the peristaltic threshold suggesting that it prevented the action of locally released 5-HT. Applied to the lumen they blocked the effect of co-administered 5-HT. LSD and 2-bromo- d-LSD were used as 5-HT antagonists. Removing the mucosa from the loop of intestine or luminal application of cocaine or procaine abolished the peristaltic reflex and under these conditions luminal 5-HT had no effect. Application of 5-HT to the bath invariably caused inhibition of peristalsis, even when this was already stimulated by intraluminal 5-HT. Adding 5-HT to the lumen dose-dependently decreased threshold with a threshold concentration around 1 n m. In the guinea-pig ileum peristalsis was triggered initially by a pressure rise of just 1–1.5 cmH 2O, rising to about 2 cmH 2O after an hour or so. Their major findings can be summarized as follows. ![]() Yet, with cleverly designed protocols and enormous insight Bülbring and Lin established a concept for control that still holds 50 years later. The paper is also very descriptive so that the reader can get a real feel for the whole study design, problems that were encountered and overcome, variability in responses and there's not a P value in sight. Assay for endogenous 5-HT was based on strips of rat stomach, uterus and colon rather than HPLC or amperometry. Limited pharmacological tools reflect the lack of appreciation at the time of the range of 5-HT receptor subtypes that are now known to be expressed in the gut mucosa and which influence sensory signalling. Reading again about kymographs and ‘home-made’ piston and float recorders to monitor pressure and volume contrasts with modern descriptions of solid-state electronics, digital devices and computer analysis. This classic paper describes the methodological developments that were necessary to record the propulsion of luminal contents by pressure-evoked peristalis in the guinea-pig ileum (and rabbit jejunum) during application of 5-HT to the lumen, and gives a detailed account of experiments designed to unravel the role of 5-HT in sensory signalling.įirst, a word or two about the available methodology. Bülbring and Lin therefore set out to ask the beautifully simple question – what happens if 5-HT is applied not to the serosa but to the mucosa? Their hypothesis was that this would mimic release of endogenous 5-HT which in turn would activate receptors associated with mucosal sensory mechanisms. In contrast, when 5-HT was applied to isolated intestinal segments in an organ bath it inhibited or abolished the peristaltic reflex ( Kosterlitz & Robinson, 1957). Carcinoid syndrome, in which there is massive outpouring of 5-HT from mucosal enterochromaffin cells, is characterized by increased intestinal activity and diarrhoea. However, there was also something of a dilemma. It was also evident that there was a rich source of 5-HT in the gastrointestinal tract and that this was mainly within the mucosal epithelium ( Feldberg & Toh, 1953). ![]() They had also demonstrated that the peristaltic reflex could be triggered by distension, but required a sensory mechanism within the mucosa since it was lost after removal of the mucous membrane or following topical application of local anaesthetic. It serves as a who's who in serotonin research and catalogues the development of our understanding of the role that 5-HT plays in sensory signalling from the gut lumen.īülbring had already shown in early publications that the peristaltic reflex was entirely mediated by neural mechanisms within the bowel wall since degenerative section of the extrinsic innervation had no effect on reflex activity ( Bülbring et al. It is interesting to look through the citation records of classic papers such as this – Bülbring & Lin (1958). ![]()
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