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Recording from human gut tissue: a major step towards more efficient drug development?
  1. Michael Schemann
  1. Correspondence to Professor Dr Michael Schemann, Human Biology, Technische Universität München, Liesel-Beckmann-Strasse 4, 85350 Freising, Germany; schemann{at}wzw.tum.de

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Translational research is a rewarding challenge and of major relevance for the field of gastroenterology, in particular neurogastroenterology, in our endeavour to improve treatment of patients suffering from functional, inflammatory or structural gut disorders. Although in vivo and in vitro animal models have provided insights into potential mechanisms of gut disorders and identified putative drugs targets, these often failed to translate into successful treatments in humans. There are many reasons for this failure such as limited bioavailability, low efficacy of drugs or safety issues. While these obstacles are intrinsic to every drug development programme it is species specific action of endogenous mediators or expression of signalling cascades that restrict translation of data from animal models to human conditions. This, however, is an issue that can be tackled by developing new techniques or adapting existing methods from animal studies to investigate receptor expression, pharmacology of signalling molecules and intracellular pathways involved in drug actions on behaviour of human gut tissue.

Measurements of gastrointestinal functions, in particular motility and transit, are routinely performed in healthy volunteers and patients.1 2 While such studies provide important information on the nature of motor disorders or the efficacy of a drug to alter gastrointestinal transit they are not suitable to characterise the modes of action of drugs or to identify novel targets to treat a particular pathology. This requires experiments in isolated gut tissue which derives from bowel resections or biopsies obtained during endoscopy.

Recordings from human isolated gut tissues have provided information on the effects of drugs on secretion,3 motility4 or enteric nerve activity,5 to mention only a few examples. Beyond revealing novel insights these types of studies also reveal human tissue specific action of mediators. One striking example is the ability of 5-HT3 receptor antagonists to modulate peristaltic reflex …

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