Regulation of gastrointestinal function
The mechanical and chemical processes of digestion are controlled by an extremely complex regulatory system that is only partially understood at present. The occurrence of digestive events in a sequential, coordinated manner is controlled by a regulatory network that is currently believed to involve several different but apparently overlapping functions performed by the endocrine, paracrine, and neurocrine systems. Each system uses chemical messengers that are derived from amino acids, mostly peptides and monoamines. The three systems differ mainly in the mechanism by which the messenger is delivered to target cells.
In addition to containing enzyme-secreting glaJ the walls of the gastrointestinal tract are highly iru vated, and the mucosal lining consists of a mutun many cell types with different structural features relc to their principal function, either absorptive, secretoIY regulatory. Although absorptive cells predominate in lining of the small intestine, other types of cells are persed among them,with access to stimuli from components of the intestinal lumen and neural and hormonal stimuli. Endocrine cells are found throughout the intestinal tract but are especially concentrated in the antrum of the stomach, duodenum, and the upper small intestine. Like the absorptive cells, the luminal side of the endocrine cells may have microvilli, which sense the luminal stimuli. These cells have secretory granules, which contain the peptide hormone specific to the cell type sorne may also contain a biogenic amine, such as histamine or serotonin. Under the influence of specific stimuli, the endocrine cells release the hormone to the blood, illereby sending messages through the systemic circulation to the target cells, which have specific receptors for a particular hormone.
The cells of the paracrine system employ similar messengers, but their action is restricted to target cells within the reach of the messenger by diffusion through inter cellular space. It appears that the reach of paracrine cells may be extended by the presence in some cells
cytoplasmic extensions (resembling the processes of the neurons), which can deliver their messenger past several ontarget cells. The paracrine regulation is local and resembles the neurocrine-mediated regulatory action, fuch also is restricted to a short distance covered by the synaptic cleft. The three regula tory systems may have join t separate target cells. In the former instance, separate receptor sites are involved. However, for reasons not un erstood, the effects of the messengers delivered by the dllferent systems are interdependent and frequently result in potentiation of the regulatory response. Overlaping between the systems is indicated also by the fact that :;orne cells may release both an endocrine and a paracrine :nessenger or that the same substance may be produced more than one system. As a result, many of these regulatory agents are not hormones according to the strict definition of the term.1,2
The complexity and interdependence of the regula-my actions of the neuro-, endo- and paracrine systems are best demonstrated by their roles in gastric acid procuction. The three best understood stimulants of gastric hydrochloric acid production are acetylcholine (neurocrine), gastrin (endocrine), and histamine (paracrine), each of which acts at a different receptor site of the ;xrrietal cells. However, the combined effect of the three exceeds the secretory response expected from their indi-idual potencies. Furthermore, agents that are specific inhibitors of certain stimulants in vitro may be nonspecific in vivo. For example, anticholinergic agents not only inhibit the effects of cholinergic stimulants but also reduce the secretory response to gastrin. Cimetidine,which is a specific blocker of H2 receptors involved in histamine-stimulated acid production (regular antihistaminic agents block HI receptors), also inhibits gastrin in action, and its inhibition is further augmented by Smultaneous administration of anticholinergic agents.This general action makes cimetidine a useful therapeutic agent for prevention of excessive gastric acid production.
The production of other digestive juices and gastrointestinal motility also are regulated by multiple mechanisms, and the functions of the various agents are overlapping. Summarizes the functions and stimuli of the currently known major gastrointestinal peptides and other regulatory substances. It should be noted that effects produced in vitro by a high concentration of a substance may not represent the physiological role of the subtance. Also, as indicated, many substances previously considered to function only in the GI tract may have regulatory roles elsewhere in the body as well.
