Publisher Summary

This chapter presents a survey of the gastrointestinal hormonology. Most of the gastrointestinal hormones appear to have effects that are localized to the gut. Each of the gastrointestinal hormones is a polypeptide whose effects depend on its molecular structure. Gastrin and cholecystokinin (CCK), for example, possess identical four-amino residues at the carboxyl terminal of the polypeptide chain and have similar stimulant effects on the stomach, gall bladder, and pancreas. This residue alone is capable of producing the effects of the full molecule although not to the same degree. Similarly, the effect of CCK on the oxyntic—acid-secreting—cells of the stomach is not nearly as strong as the effects of equal amounts of gastrin even though it appears to have a stronger affinity for surface receptors on these cells. Because of this, equimolecular doses of CCK inhibit the full effect of gastrin in the secretion of acid. While hormones of the secretin family also have structural and functional similarities, the entire molecule is required to induce the key physiologic responses. These hormones include secretin, vasoactive intestinal polypeptide, gastric inhibitory polypeptide, and glucagon.

Table 2-1

Gastrin-Cholecystokinin Family

Table 2-2

The Secretin-Glucagon Family

Secretin (27 amino acids, mol wt 3,055)

His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Glu-Leu-Ser-Arg-Lev-Arg-Asp-Ser-Ala-Arg-Leu-Gln-Arg-Leu-Leu-Gln-Gly-Leu-Val-NH2

Glucagon (29 amino acids, mol wt 3,484)

His-Ser-Gln-Gln-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asp-Thr

Vasoactive intestinal peptide (28 amino acids, mol wt 3,326)

His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn-NH2

Gastric inhibitory polypeptide (43 amino acids, mol wt 5,104)

Tyr-Ala-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-Ala-Met-Asp-Lys-Ile-Arg-Gln-Gln-Asp-Phe-Val-Asn-Trp-Leu-Leu-Ala-Gln-Gln-Lys-Gly-Lys-Lys-Ser-Asp-Trp-Lys-His-Asn-Ile-Thr-Gln

Other Gastrointestinal Peptides

Motilin (22 amino acids, mol wt 2,698)

Phe-Val-Pro-Ile-Phe-Thr-Tyr-Gly-Glu-Leu-Gln-Arg-Met-Gln-Glu-Lys-Glu-Arg-Asn-Lys-Gly-Gln

Pancreatic polypeptides (36 amino acids, mol wt 4,226)

Ala-Pro-Leu-Glu-Pro-Gln-Tyr-Pro-Gly-Asp-Asp-Ala-Thr-Pro-Glu-Gln-Met-Ala-Gln-Tyr-Ala-Ala-Glu-Leu-Arg-Arg-Tyr-Ile-Asn-Met-Leu-Thr-Arg-Pro-Arg-Tyr-NH2

Somatostatin (14 amino acids, mol wt 1,639)

H-Ala-Gly-Gys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH

Bombesin (14 amino acids, mol wt 1,620)

Glp-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2

Source: Go VLW, Owyang C. Radioimmunoassay of gastrointestinal hormones. In: Glass GB, ed. Progress in Gastroenterology, vol 3. New York: Grune and Stratton, 1977:156. Reprinted by permission.

PRESUMED MECHANISM OF HORMONAL ACTION

Peptide hormones bind to specific receptors on target cell membranes. This first step in mediation of the effect of the hormone on specific cells has been demonstrated in a number of instances, examples of which are the binding of 125I-gastrin to canine antral smooth muscle, and of 125I-secretin to hepatocytic plasma membranes. Binding alone is only a first step, since nonspecific or inhibitory binding may also occur. Some further alteration of target cells, proportional to the amount of hormonal binding, must occur—the hormonal response. One such measurable response is the intracellular activation of the enzyme adenylate cyclase at cellular membranes, with the resultant production of adenosine 3′5′-monophosphate (cyclic AMP) from cytoplasmic adenosine triphosphate (ATP). But Gardner (1979) has pointed out that this response may not correlate with the observed functional changes in the cell, and that target cells may respond to stimulation with specific hormones by means other than the generation of cAMP. However, where hormone binding, cAMP release, and effector cell responses all occur proportionately and at the same time in the same system, a clear cause and effect relationship can be assumed. Since these conditions have been met infrequently in the case of gastrointestinal hormones, our understanding of their mechanisms of action is only presumptive at present. The variety of actions attributable to gastrointestinal hormones is summarized in Table 2-3.

ESTABLISHED GASTROINTESTINAL HORMONES

Secretin, CCK, and gastrin have been identified, characterized, and proved to have important physiologic significance. They are thus agreed to be established gastrointestinal hormones. Since pancreozymin has been found to be identical to CCK, it is no longer considered as a separate hormone.