In the beginning of this century physiology witnessed the creation of a new concept, the hormonal regulation of the work of the digestive organs. It was found that such essential functions as the flow of pancreatic juice and emptying of bile into the intestine were regulated by two hormones, secretin and cholecystokinin, respectively. Already in 1925 French authors attempted to measure the functional capacity of the exocrine pancreas by means of stimulation with secretin. The use­ fulness of the secretin test in this connection was definitely established by Scandinavian workers in the 1930's. In spite of the difficulties in obtaining secretin American authors succeeded in keeping the interest in the secretin test alive. The development in the 1950's of counter-current, ion exchange and chromato­ graphic techniques offered new possibilities in this field. The intestinal hormones were known to be relatively low molecular peptides and these could now be isolated in pure form. Thus secretin was isolated in 1961, and cholecystokinin in 1964. The newly developed methods for peptide analysis likewise soon brought us full information about the primary structure of the peptides. Gastrin, the specific stimulant of the gastric acid secretion, which was discovered in 1905 and acknowledged as a hormone in 1938, was the first of the gastrointestinal hormones for which the structure became known. This was in 1964. Synthesis soon followed. These developments are reviewed in the first chapter of the present volume.

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I Secretin and Cholecystokinin (CCK). With 42 Figures.- A. Secretin.- I. Secretin.- 1. The Exocrine Function of the Pancreas and the Discovery of Secretin.- 2. Purification and Isolation of Secretin.- 3. The Chemical Structure of Secretin.- 4. Synthesis of Secretin.- II. Cholecystokinin (CCK).- 1. The Discovery of Cholecystokinin.- 2. The Isolation of Cholecystokinin.- 3. Chemical Structure of CCK.- 4. Urocholecystokinin.- 5. The "Pancreozymin" Activity of Cholecystokinin.- 6. Terminology, Cholecystokinin (CCK) or Cholecystokinin-Pancreozymin (CCK-PZ).- B. Common Aspects on the Gastrointestinal Hormones.- I. Common Features in the Chemical Structure of the Gastrointestinal Hormones.- 1. Secretin-Glucagon.- 2. Gastrin-Cholecystokinin-Caerulein.- 3. Cholecystokinin-Thyrocalcitonin.- 4. Amidation of the C-Terminal Carboxyl Group.- II. Biologically Active Breakdown and Synthetic Products.- 1. Secretin and Glucagon.- 2. Cholecystokinin.- 3. Gastrin and Caerulein.- 4. The Importance of the Tyrosine Ester Sulfate for the Biological Activity.- III. The Occurrence and Distribution of the Hormones in the Gastrointestinal Tract.- 1. Secretin.- 2. Cholecystokinin.- 3. The Distribution of Gastrin.- 4. The Cell Layer of the Mucosa Carrying Secretin and Gastrin.- 5. Subcellular Distribution.- IV. The Release of the Gastrointestinal Hormones.- 1. Neural Influences on the Release of the Gastrointestinal Hormones.- 2. Chemical Stimuli for the Release of Secretin and CCK.- 3. Ionic Mechanisms for the Accumulation and Release of Secretin, Gastrin and CCK.- 4. Absorption from the Intestine.- V. The Disappearance of the Gastrointestinal Hormones from the Circulating Blood.- 1. Half-life Times.- 2. Loss of Secretin during Passage through the Liver.- 3. The Fate of CCK, Gastrin, Pentagastrin and Glucagon during Passage through the Liver.- C. Biological Actions of the Gastrointestinal Hormones.- I. Actions of the Gastrointestinal Hormones on the Pancreas.- 1. Oxygen Consumption of the Pancreas under the Influence of Secretin and Cholecystokinin.- 2. Action of Secretin on the Pancreatic Blood Flow.- 3. The Action of Secretin, CCK, Gastrin and Glucagon on the Pancreatic Secretion.- II. Secretin, Glucagon, CCK and the Brunner's Glands.- III. Action of the Gastrointestinal Hormones on the Liver and the Gallbladder.- 1. The Influence of the Hormones on the Bile Flow.- 2. Action of CCK, Gastrin, Glucagon and Secretin on the Gallbladder.- IV. Influence of Secretin, CCK and Glucagon on Gastric Secretion.- 1. The Acid Secretion from the Stomach.- 2. Hormonal Influences on the Secretion of Pepsin.- V. Potentiation of the Effect of the Gastrointestinal Hormones.- VI. The Action of Secretin, CCK, Gastrin and Glucagon on Gastric Motility.- 1. Secretin.- 2. Cholecystokinin.- 3. Gastrin.- 4. Glucagon.- VII. Influence of CCK on the Sphincter of Oddi and on Intestinal Peristalsis.- 1. The Sphincter of Oddi.- 2. A Neural Component in the Action of CCK on the Intestine.- 3. The Action of Gastrin, Caerulein and Glucagon on the Intestine.- 4. Cholecystokinin for the X-Ray Analysis of the Jejuno-Ileum.- VIII. Miscellaneous Biological Effects of Secretin and Cholecystokinin.- 1. The Diuretic Effect of Secretin and Glucagon.- 2. The Release of Insulin.- 3. Release of Free Patty Acids.- 4. The Influence of Secretin and CCK on the Thoracic Lymph Flow.- 5. Toxic Effects of Secretin and Cholecystokinin Preparations.- D. The Bioassay of Secretin and Cholecystokinin.- I. The bioassay of secretin.- 1. In dogs.- 2. In cats.- 3. In rats.- 4. Secretin standards.- 5. The levels of strength of the different secretin units and standards.- II. On the bioassay of cholecystokinin preparations.- 1. The choice of unit.- 2. Determination of the Ivy dog unit.- 3. The Ljungberg technique with the guinea pig gallbladder in situ.- 4. The Amer and Becvar technique with strips of rabbit gallbladder in vitro.- 5. The assay of "pancreozymin" activity.- 6. Urocholecystokinin.- References.- II The Synthesis of (Porcine) Secretin. With 6 Figures.- A. Introduction.- B. Strategies.- C. Attempted Synthesis of Secretin on a Solid Support.- D. Synthesis of Secretin by the Stepwise Approach (Through Isolated Intermediates).- E. Synthesis of Secretin by Fragment Condensation.- F. The Conformation of Secretin.- G. Conclusions.- References.- III The Secretory Process in the Pancreatic Exocrine Cell: Morphologic and Biochemical Aspects. With 16 Figures.- A. Route and Timetable of Intracellular Transport in Resting Exocrine Cells.- B. Metabolic Requirements for Intracellular Transport over the RER-Condensing Vacuole-Pathway (steps 2-4).- C. Metabolic Aspects of Condensing Vacuole Transformation.- D. Studies on Zymogen Granule Discharge.- I. Radioassay for Zymogen Discharge.- Assumptions Involved in the Interpretation of the Radioassay.- 1. Source of Discharged Proteins.- 2. Effect of Secretogogues on Rates of Protein Synthesis and of Intracellular Transport.- E. Metabolic Requirements for Zymogen Granule Discharge.- References.- IV The Secretin Test. With 7 Figures.- A. General Introduction.- I. Secretin.- II. Pancreozymin-Cholecystokinin.- B. The Secretin Test of Pancreatic Function.- I. Physiologic Effects of Secretin.- II. Historical.- III. Methodology of the Secretin Test at Mount Sinai Hospital.- IV. Variants of the Secretin Test.- V. The Submaximal Secretin Test: Normal Results.- VI. The Maximal Secretory Response of the Pancreas to Secretin.- VII. The Effect of Age and Sex on Pancreatic Secretion.- VIII. Effect of Route of Administration of Secretin.- IX. Results with Synthetic Secretin Preparations.- X. Cytology.- XI. Results of the Secretin Test in Inflammatory and Neoplastic Disease.- C. Secretin-Pancreozymin Tests of Pancreatic Function.- I. Historical.- II. The Secretin-Pancreozymin Test.- III. The Pancreozymin-Secretin Test.- D. Serum Enzyme Tests in the Diagnosis of Pancreatic Disease.- References.- V On the Use of Cholecystokinin in the Roentgenological Examination of the Extrahepatic Biliary Tract and Intestines. With 17 Figures.- 1. Gall Bladder and Cholecysto-Cystic Junction.- 2. Sphincter of Oddi.- 3. Intestines.- References.- VI Gastrointestinal Hormones and Islet Function. With 37 Figures.- I. Introduction.- II. Historical Review.- III. Some Remarks on the Chemical Structure, Extra-insular Actions and Sites of Origin of the Gastrointestinal Hormones.- 1. Gastrin.- 2. Cholecystokinin-Pancreozymin (CC…