The endocrine versatility of the gut: general and evolutionary aspects of the active peptides of the gastrointestinal tract.

Recent years have seen an unprecedented expansion of interest in the gastrointestinal endocrine system that shows no signs of abating. In large measure this awakening can be attributed to the chemical studies that have resulted in the isolation and elucidation of structure of a wide variety of biologically active gut peptides (Gregory and Tracy, 1975; Mutt, 1976). The availability of highly purified preparations of these peptides has made possible detailed studies of their effects and mode of action at the cellular level. In addition, it has become possible to apply immunochemical methods of analysis that have helped to reveal the cellular origins of the peptides and have allowed their estimation in blood and tissue extracts. Several unexpected findings have emerged from these studies. For example, it now seems possible that some of the peptides produced by gut endocrine cells are not secreted into the blood stream, but rather act locally by diffusion to their targets through the extracellular space (paracrine effects). Furthermore, it is now clear that many of the active peptides in gut extracts originate not just in gut endocrine cells but also in nerve fibres. Peptides of the enteric plexuses are also found in the central nervous system, and other peptides previously identified in brain have since been found in the gut. These developments raise questions of fundamental importance about the interrelationships of the brain-gut peptides and their roles in health and disease that, taken together, point to the need for a re-evaluation of the system of peptide messengers as a whole. An important aspect of such an analysis is the extent to which the chemical and functional relationships of these peptides can be accounted for in evolutionary terms. The relevance of this approach is emphasised by the similarity in structure of groups of brain-gut peptides that suggest a shared ancestry, both of the molecules in question, and of the entire system of neuronal and hormonal peptides.