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Neuroendocrine interactions in the gastrointestinal tract under normal and pathological conditions

Research project P4/16 (Research action P4)

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Description :

The enteric nervous system plays a crucial role in regulating intestinal motility and secretion/absorption mechanisms in the gut. It is a largely independent, integrated system with structural and functional characteristics reminiscent of those of the central nervous system. The aim of the present network is to study neuroendocrine interactions in different segments of the gastro-intestinal tract from a morphological, functional, and pharmacological standpoint under normal and pathological conditions. To this end, the neurochemical, electrophysiological, and pharmacological characteristics of enteric neurones are studied in detail, as well as the molecular biological structural characteristics and localisation of receptors in the intestinal wall with which specific neurotransmitters and neurohormones interact.

A first aim is to expand the neurochemical codification of the various components of the enteric nervous system and to correlate these data with electrophysiological characteristics and with the localisation of specific receptors for certain neurotransmitters and neuromodulators.

A second aim is to study the role of nitric oxide (NO) and NANC (non-adrenergic non-cholinergic) neurotransmission in different intestinal segments under normal and pathological conditions.

A third objective is to elucidate the pathogenesis of intestinal lesions in schistosomiasis due to Schistosoma mansoni. This disease is a widespread helminthic disease of tropical and subtropical regions and only the corresponding liver lesions have been studied in detail so far.

A fourth aim is to study neuroendocrine changes in intestinal ischaemia and intestinal denervation.

A fifth series of experiments is related to the recent development of a new class of pharmacological agents promoting gut motility, the motilides, and focuses on motilin-mediated mechanisms in the regulation of gut motility.

The steering team (UIA) is involved in each of the above-mentioned studies. It is composed of representatives of three disciplines: cytology and histology, gastro-enterology, and pathological anatomy. The ULB handles the molecular biological aspects of each of the studies mentioned. RUG collaborates in the pharmacological work undertaken by the steering team and is in charge of the pharmacological characterization of new substances characterized by the ULB. The KUL is in charge of objective number 5 and aims to characterize the various types of motilin receptors, in close collaboration with the ULB. In collaboration with the steering team, in vivo intestinal transit is studied in laboratory animals to test the effects of motilin agonists and antagonists.

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