Peptides of the gastrointestinal tract

Some of the functions of the gastrointestinal tract are regulated by peptides, derivatives of amino acids and a variety of mediators released from nerves. These functions include contraction and relaxation of the smooth muscle wall and the sphincters (physiological 'gatekeepers' of the gastrointestinal tract); secretion of enzymes for digestion; secretion of fluids and electrolytes; and growth of the tissues of the gastrointestinal tract.

All gastrointestinal hormones are peptides, i.e. small molecules comprising up to 50 amino acids. It is important, however, to realise that not all peptides found in the digestive tract are hormones. The gastrointestinal peptides can be divided into hormones, paracrines and neurocrines, depending on the method by which the peptide is delivered to its target site.

Hormones are peptides released from endocrine cells of the gastrointestinal tract. They are secreted into the portal circulation, pass through the liver and enter the systemic circulation. The systemic circulation then delivers the hormone to target cells with receptors for that specific hormone. These target cells may be in the gastrointestinal tract itself (e.g. gastrin acts upon the parietal cells of the stomach to stimulate acid secretion), or the target cells may be located in another region of the body (e.g. gastric inhibitory peptide acts upon the P cells of the pancreas to cause insulin secretion). Several criteria must be met for a substance to qualify as a gastrointestinal hormone:

• The substance must be secreted in response to a physiological stimulus and carried in the bloodstream to a distant site, where it produces a physiological action.

• The hormone's action must be independent of any neural activity.

• The hormone must have been isolated, purified and chemically identified.

Four gastrointestinal peptides are classified as hormones: gastrin, cholecysto-kinin (CCK), secretin and gastric inhibitory peptide (GIP). These are discussed in more detail in Chapters 4 and 8.

Most paracrines, with the exception of histamine, are peptides secreted by endocrine cells of the gastrointestinal tract. In contrast to hormones, however, the paracrines act locally within the same tissue that secretes them. Para-crine substances reach their target cells by diffusing short distances through interstitial tissue, or they are carried short distances in capillaries. The only gastrointestinal peptide with a known paracrine function is somatostatin, which has an inhibitory effect throughout the gastrointestinal tract in that it reduces motility and secretion of digestive juices.

Neurocrines are synthesised in neurones of the gastrointestinal tract and are released in response to an action potential. Following release, the neurocrine diffuses across the synapse and acts upon its target cell. There are many neurocrines in the gastrointestinal tract including acetylcholine, noradrenalin and vasoactive intestinal peptide (VIP). The sources and actions of these neurocrines are summarised in Table 2.1.

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