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Histochemistry and Clinical Features of Gut Polypeptides in the Human Digestive Organs

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Histochemistry and Clinical Features of Gut Polypeptides in the Human Digestive Organs ACTA HISTOCHEM. CYTOCHEM. Vol. 13, No. 1, 1980 -SPECIAL ADDRESS I- HISTOCHEMISTRY AND CLINICAL FEATURES OF GUT POLYPEPTIDES IN THE HUMAN DIGESTIVE ORGANS TAKAYOSHITOBE Departmentof Surgery,Faculty of Medicine,Kyoto University,Kyoto 606 1. Historical reviewof the gut hormoneresearch Brief explanations are provided of the following; a. definition of gut hormones b. gut hormone and brain gut peptides c. synthesis of these polypeptides d. gut endocrinology e. enterochromaffin cell, argentaffin and argyrophylic reactivity f. APUD series g. Lausanne classification and gut polypeptides h. immunofluorescence for gut polypeptide demonstration-its techniques and problems of fixation methods 2. Distributionof gut hormones Antisera against specific synthetic gastrin (human gastrin I), secretin, CCK- pancreozymin (desulfated CCK-PZ synthesized by Yajima et al.), motilin (synthe- sized by Yajima et al.), GIP (synthesized by Yajima), and VIP (synthesized by Yajima) were prepared by immunization of albino rabbits. IgG fractions of these antisera were labeled with FITC (fluorescence isothiocyanate). A direct immunofluorescent technique was used to investigate the distribution of gastrin, secretin, CCK-pancreozymin, motilin, GIP and VIP. Brain gut peptides, somatostain and substance P were also investigated by the same method. a. Gastrin Gastrin-containing cells were observed in the antrum of the human stomach (Fig. 1) and in the doudenum. No gastrin-containing cells were seen in the body or cardia of the stomach, jejunum, ileum, colon or pancreas (Fig. 2). b. Secretin The distribution of secretin in the human digestive organs was as follows (Fig. 3): c. CCK-pancreozymin CCK-pancreozymin-containing cells were observed in the deeper zone of the duodenum near Brunner's glands)(Fig. 4). Fig. 5 shows their distribution in the human digestive organs. d. Motilin As already noted in the previous report, argentaffin and argyrophilic are motilin- 2 GUT POLYPEPTIDES 3 FIG. 1. Gastrin-containingcells in human stomach. containing cells. The characteristic features of their histochemistry are those of enterochromaffin cells. The distribution of motilin-containing cells (Fig. 6) is limited in comparison with that of 5-HT-containing enterochromaffin cells (Fig. 7). e. GIP and VIP See Polak's articles. f. Somatostatin and gastrin The brain gut peptide somatostatin is known to be present in large amounts in the stomach and pancreas. Its halflife in the body is less than three min when it is administered exogenously and it is considered to he a paracrine rather than an endocrine substance. Its main effect is on adjacent tissue or cells. In the pancreas, somatostatin, which is present in D cells, inhibits not only exocrine secretion but also endocrine, i.e. glucagon and insulin, release. In the stomach it has been observed in the antrum. Somatostatin inhibits not only exo- crine, acid and pepsinogen secretion, but also endocrine gastrin release. With the direct double-staining method of immunofluorescence, -FITC- labeled somatostatin antiserum and TRITC-labeled gastrin antiserum-the location TOBE FIG. 2. FIG. 3. GUT POLYPEPTIDES 5 FIG. 4. CCK-PZ containing cellsin human duodenum. of these two polypeptides was demonstrated. As shown in Fig. 8, somatostatin-containing cells (yellow green-FITC fluo- rescence) were located among the gastrin-containing cells (orange-TRITC fluo- rescence) in the same crypt. This histological finding suggests that somatostatin inhibits gastrin release only from the adjacent gastrin-containing cells and that it is not an endocrine but a paracrine substance. 3. Organ (Entero-pancreatic-hepatic)interaction via gut peptides As is shown in Fig. 9, hydrochloric acid secreted by parietal cells, which are stimulated by gastrin or by the vagal nerve, stimulates secretin release from S cells in the duodenum. Secretin stimulates sodium bicarbonate and water secretion from the duct cells of the pancreas-pancreatic juice is only one inhibitor of secretion release by S cells. Hydrochloric acid also activates pepsinogen to pepsin, which digests proteins 6 TOBE FIG. 5. FIG. 6. FIG. 7. GUT POLYPEPTIDES 7 FIG. 8. Gastrin and somatostatin in human stomach. to peptone. Peptone is the strongest releaser of CCK-PZ from CCK-PZ-containing cells in the duodenum. And CCK-PZ stimulates enzyme (trypsinogen, lipase and amylase secretion from the acinar cells of the pancreas. CCK-PZ, secretin, glucagon, VIP and GIP are all distributed in the duodenum and stimulate insulin release from the Isles of Langerhans in the pancreas. Insulin stimulates the pancreozymin effect in the pancreas. Moreover, insulin is the strongest hepatotrophic factor. These findings indicate one pattern of organ interactions (entero-pancreatic. pancreato-hepatic, among gut polypeptides. 8 TOBE FIG. 9..
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