Neurohormonal control of intestinal transit L Bueno, Jean Fioramonti To cite this version: L Bueno, Jean Fioramonti. Neurohormonal control of intestinal transit. Reproduction Nutrition Development, EDP Sciences, 1994, 34 (6), pp.513-525. hal-00899677 HAL Id: hal-00899677 https://hal.archives-ouvertes.fr/hal-00899677 Submitted on 1 Jan 1994 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Neurohormonal control of intestinal transit L Bueno J Fioramonti INRA, Department of Pharmacology, BP 3, 31931 Toulouse, France Summary ― This review shows that numerous neuropeptides and hormones are involved in the reg- ulation of intestinal transit. Many gastrointestinal hormones known to act on smooth muscle to influence muscle contractility also play a role in the genesis of abrupt changes associated with alimentary behaviour. In many monogastrics and ruminants, the cyclic occurrence of the migrating motor complex (MMC) is linked to peripheral hormonal factors only slightly influenced by the nature of food. Motilin is the major homone involved in triggering the gastric migrating motor complex while somatostatine and enkephalins are implicated in the propagation along the small intestine. Other hormones, like CCK8, insulin, gastrin, and neurotensin, trigger the development of an intestinal feed pattern but CCK released at the central nervous system ventromedial hypothalamus is involved in maintaining the postprandial type of activity. Gastrointestinal transit may be altered in physiopathological situations in which CRF, TRH and some cytokines (IL1 1!, TNFa) play an important role. gastrointestinal tract / colon / motility / transit / hormone / neuropeptide / brain / motilin / CCK Résumé ― Contrôle neuro-hormonal du transit intestinal. De nombreux peptides et hormones diges- tives sont impliqués dans la régulation du transit intestinal. Ils agissent soit directement sur la cellule musculaire lisse, soit possèdent des sites d’action relevant de l’innervation intrinsèque mais peuvent agir également au niveau supraspinal où ils sont responsables des adaptations motrices rapides en réponse à des stimuli externes tels que la prise alimentaire. Chez la plupart des monogastriques et chez les ruminants, l’apparition de cycles réguliers d’activité motrice que constituent les complexes moteurs migrants (CMM) est liée à des variations cycliques de la libération d’une hormone digestive : la moti- line, indépendemment de facteurs alimentaires externes. La propagation de cette activité est sous le double contrôle de la somatostatine et des enképhalines. D’autres hormones telles que la CCKB, l’in- suline, la gastrine et la neurotensine sont impliquées à plusieurs niveaux pour initier le profil d’activité postprandiale mais la CCK libérée au niveau de l’hypothalamus ventromédian intervient de façon pri- vilégiée pour maintenir ce profil pendant toute la phase digestive. Enfin, récemment, il a été montré que les altérations motrices dans des situations physiopathologiques relèvent de l’intervention de pep- tides spécifiques (CRF, TRH) ou de certaines cytokines (IL 1{3, TNFa) dont les mécanismes d’action ne sont pas totalement élucidés. appareil digestif / côlon / motricité / transit / hormones / neuropeptides / fibres / motiline / CCK l aliments INTRODUCTION neurons in vagal nerves (Abrahamsson, 1973), which enables it to accomodate food The major function of the intestine is to digest delivery by the cesophagus. The contrac- food, assimilate nutrients and expel non- tions of the corpus and the antrum are coor- digestible residues. These functions are dinated and a slow contraction of the cor- directly related to its motility which is respon- pus lasting approximately 30 s is associated sible for the intestinal delivery and transport with 3-5 more rapid contractions of the of digesta. antrum (Gill et al, 1985). After a meal, the is The fact that feeding affects gastro- digestive pattern characterized by steady intestinal motility has been known since the low-amplitude contractions (4-5 per min) in last century when Beaumont (1833) the gastric antrum with no significant motor described the changes in amplitude and fre- activity in the gastric body. quency of gastric contractions associated A cyclic pattern of gastric motility has with feeding. From 1940, improvements of been found in the dog (Itoh et al, 1977) and our knowledge of mechanical events occur- in man (Rees etal, 1982). In the rat (Bueno ring in the digestive tract were associated et al, 1982) and the rabbit (Deloof and with the development of manometric methods Rousseau, 1985) there is no cyclic organi- which permitted the recognition of the major zation of the gastric motility, and feeding patterns of gastrointestinal motility. However,r, induces an increase of both the amplitude a major step was linked to the use of elec- and frequency of the contractions. tromyographic techniques, which have allowed a clear identification of the charac- teristics of the fasted pattern, ie the migrating Small intestine motor (or myoelectric) complex (MMC) in and in other animal dogs (Szurszewski, 1969) The basic motor pattern of many animal species (Bu6no et al, 1975; Ruckebusch and species investigated consists of MMCs, first it has been Fioramonti, 1975). Recently, identified as &dquo;a caudad band of large-ampli- shown that the motor changes associated tude action potentials starting in the duode- with are related to the nature of food feeding num and traversing the small bowel&dquo; and caloric intake and that some peptides (Szurszewski, 1969). Each MMC corre- play a specific role in their genesis. sponds to 3 consecutive phases: phase 1 has little or no contractile activity (quiescent phase), phase 2 has intermittent and irregular PATTERNS OF MOTILITY contractions, while the contractions of phase AND DIGESTIVE STATUS 3 occur at their maximal rate, which is deter- mined by the frequency of the slow waves. The duration of phase 3 activity is relatively Stomach constant, but that of other phases varies from cycle to cycle, depending on the flow of In many species, manometric recordings of digesta (Ruckebusch and Bueno, 1977). antral motility during fasting or interdiges- Depending on the animal species, the MMC tive periods exhibit a cyclic pattern of high- cycle length varies between 60 and 120 min amplitude contractions grouped in phases (Bueno and Ruckebusch, 1978) except in separated by periods of quiescence and rats in which MMCs recur at 15-20 min inter- appearing at 90-120 min intervals. The vals (Ruckebush and Fioramonti, 1975). important property of the proximal stomach Feeding is accompanied by a disruption is receptive relaxation, mediated by inhibitory of the intestinal MMC to give a ’postprandial’ pattern characterized by the irregular occur- faeces in pellets, such as the rabbit or the rence of contractions similar to those sheep (Fioramonti, 1981).). observed during phase 2 of the MMC The typical characteristic of colonic motil- et Code and (Bueno al, 1975; Marlett, ity in man, not seen in animals, consists of 1975). a very low activity during the night (Frexi- This disruption of the MMC pattern is nos et al, 1985). After a 3 000-4 000 kJ related to the energy content of the meal, meal the frequency of colonic contractions is the nature of nutrients and the frequency increased for 2-3 h. Such an increase in of meals. However, non-nutrient factors are colonic motility after a meal seems to be a also involved in the postprandial disruption common feature. of the MMC pattern, since sham-feeding delays the next phase 3 in man (Defilippi and Valenzuela, 1981). On the other hand, RELATIONSHIPS BETWEEN MOTILITY meal frequency modulates the effects of AND FLOW OF DIGESTA feeding on small intestinal motility. For example, in pigs (Ruckebusch and Bueno, 1976) and in rats (Ruckebusch and Ferre, Stomach 1973) ingestion of a daily large meal dis- rupts the MMC for several hours, while In terms of transit of digesta, the 3 major under ad libitum feeding the MMC fre- functions of the stomach are the receipt of quency is similar to that observed in the food, the storage of ingested food and the fasted state. However, in adult and neona- emptying of liquids and solids. tal pigs, feeding a standard meal only induces a 1-h delay in the onset of the next The entry of a large amount of food into phase 3 (Burrows et al, 1986; Rayner and the stomach leads to adaptive (or recep- Wenham, 1986). tive) relaxation of the proximal part of the stomach acting as a reservoir (Jahnberg, 1977). The rhythmic contractions of the dis- Large intestine tal stomach are thought to control the tritu- ration and emptying of solids, whereas the tonic contractions of the proximal stomach A common feature of the colon in all mam- govern the rate of emptying of liquids. The malian is a of species investigated duality pylorus prevents duodenogastric reflux, but the contractile activity: tonic contractions is also a true sphincter which controls the to myoelectrical events char- corresponding empyting of food from the stomach. acterized