Characteristics Of Gastrointestinal Peptides

The GI peptides regulate many different functions: water and electrolyte secretion from the stomach, pancreas, liver, and gut; enzyme secretion of the stomach and pancreas; and contraction and relaxation of the smooth muscle of the stomach, small and large bowel, various sphincters, and gall bladder. These peptides also regulate the release of GI peptides and some other endocrines, such as insulin, glucagon, and calcitonin. Some GI peptides have trophic effects, regulating the growth of the exocrine pancreas and the mucosa of the stomach, small and large intestine, and gall bladder. Many peptides have identical effects on an end organ. Others may produce opposite effects.

Thus, the end-organ response is an integration of the actions of the various peptides reaching its receptors. Fortunately, many of these effects are pharmacologic and are produced by doses of peptide greater than those present as a result of normal release. The important actions of the GI peptides are the physiologic ones— those that occur with amounts of hormone released as a result of the stimulus provided by the ingestion and digestion of a meal. The actions of the GI peptides also vary in intensity and direction among species. Wherever the data are available, the remainder of this section concerns the actions that occur in humans.

Although some GI peptides are located in nerves, many others are found in mucosal endocrine cells. These cells are found not in discrete isolated glands but as single cells scattered over a wide area of mucosa. This more generalized distribution ensures that endocrine release is regulated by the events taking place in a relatively large part of the gut. Thus, the release of these peptides is an integrated response in time as well as area. Because the gut endocrine cells are scattered, one cannot surgically remove a GI ''endocrine gland'' to examine the effects of the absence of these peptides—a standard technique of endocrinologists to determine the physiologically significant actions of hormones. This distribution also means that studies of the release of these

Longitudinal Circular Muscularis Mucosa

Muscle Muscle Mucosae

Longitudinal Circular Muscularis Mucosa

Muscle Muscle Mucosae

Sympathetic Myenteric Submucosal

System Plexus Plexus

FIGURE 3 The integration of the extrinsic (parasympathetic and sympathetic) nervous system with the enteric (myenteric and submucosal plexuses) nervous system. The preganglionic fibers of the parasympathetic synapse with ganglion cells located in the enteric nervous system. Their cell bodies, in turn, send signals to smooth muscle, secretory, and endocrine cells. They also receive information from receptors located in the mucosa and in the smooth muscle, which is relayed to higher centers via vagal afferents. This may result in vagovagal (long) reflexes. Postganglionic efferent fibers from the sympathetic ganglia innervate the elements of the enteric system, but they also innervate smooth muscle, blood vessels, and secretory cells directly. The enteric nervous system relays information up and down the length of the GI tract, which may result in short or intrinsic reflexes.

Sympathetic Myenteric Submucosal

System Plexus Plexus

FIGURE 3 The integration of the extrinsic (parasympathetic and sympathetic) nervous system with the enteric (myenteric and submucosal plexuses) nervous system. The preganglionic fibers of the parasympathetic synapse with ganglion cells located in the enteric nervous system. Their cell bodies, in turn, send signals to smooth muscle, secretory, and endocrine cells. They also receive information from receptors located in the mucosa and in the smooth muscle, which is relayed to higher centers via vagal afferents. This may result in vagovagal (long) reflexes. Postganglionic efferent fibers from the sympathetic ganglia innervate the elements of the enteric system, but they also innervate smooth muscle, blood vessels, and secretory cells directly. The enteric nervous system relays information up and down the length of the GI tract, which may result in short or intrinsic reflexes.

hormones are difficult, because in vitro experiments are impossible and there is often no venous blood supply to isolate and sample.

At first it was believed that all GI peptides were hormones. Although all GI hormones are peptides, we now know that the GI peptides can be classified as endocrine hormones, paracrines, or neurocrines (Fig. 4).

Hormones are released into the portal circulation, pass through the liver, and are then circulated to all tissues of the body (unless excluded from the brain by the blood-brain barrier). Target tissues are those that have specific receptors for the hormones in their plasma membranes. Thus, specificity is a property of the target tissue. Paracrines are released from endocrine cells within the mucosa and diffuse through the extracellular spaces or are carried short distances by capillaries to their target cells. Here, specificity depends not only on the presence of receptors but also on the proximity of the target cell to the endocrine cell. Thus, the effects of paracrines are limited by diffusion, but because the releasing cells may be spread over a large area of mucosa it is still possible for paracrines to act as major mediators of function. Histamine, a derivative of the amino acid histidine, is an important agent in the stimulation of gastric acid secretion that acts as a paracrine.

Neurocrines are synthesized in the cell bodies of neurons and migrate to the axonal ending, where they can be released by an action potential. Once released, neurocrines diffuse the short distance across the synaptic cleft to their target cells. Acetylcholine, although not a peptide, is the best known neuroregulator in the GI tract.

Paracrine

Paracrine

FIGURE 4 Different methods of delivery of peptides from cells of the GI tract. BV, blood vessel; EC, endocrine cell; N, neuron; P, peptide; TC, target cell.
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