The neuroendocrine system of the gut

The digestive tract is the richest source of regulatory peptides outside the brain. Such peptides occur all along the gut in the neuroendocrine system which is composed of endocrine/paracrine cells disseminated in the epithelium and of intrinsic neurons that form continuous ganglionic chains in the submucosa and in the muscle layer. Some endocrine/paracrine cells, particularly in the stomach, still have not been associated with an identified regulatory peptide implying that our present knowledge is far from complete. The intracellular processing of regulatory peptide precursors involves multi-step proteolytic cleavage generating several fragments. In many instances more than one biologically active peptide is generated from one and the same precursor. In addition, certain endocrine/paracrine cells and neurons have been found to produce more than one peptide precursor and some are known to harbour 'classical' neurotransmitters, such as 5-hydroxytryptamine, histamine and GABA as well as regulatory peptides. Key questions for the future are the functional significance of the coexistence of multiple messengers within the same cells and the details of how the endocrine/paracrine cells and the neurons in the gut interact.