The discovery of hypothalamic factors that inhibited growth hormone secretion and of pancreatic factors that inhibited insulin secretion were the first clues to the existence of somatostatin. During the course of efforts to isolate growth hormone releasing factor, Krulich, McCann and Dhariwal found that hypothalamic extracts contained a potent inhibitor of growth hormone secretion. They postulated that growth hormone secretion was under a dual control system, one inhibitory and the other excitatory (I) . In studies being carried out at about the same time, Hellman and Lernmark found a factor in pancreatic extracts that inhibited insulin secretion (2). They postulated that islet cell function was regulated by local hormonal factors. With the isolation and chemical characterization of somatostatin by Brazeau and colleagues (3), and the availability of relatively large amounts of the synthetic peptide for research, it has been possible to demonstrate that both predictions were true. Subsequent work revealed that somatostatin, as initially isolated (somatostatin 14), was but one of several related peptides, part of a multigene family, with tissue specific processing. Many of the details of biosynthesis and genetic control have been worked out, and this molecule has served many workers as a model gut-brain peptide for detailed study. The peptides are widely distributed in tissues and exert an extraordinary range of effects on most glandular secretions, both internal and external.

Inhalt

I. Biosynthesis and Processing.- 1. Regulation and Diversity of Peptide Hormone Gene Expression.- 2. Structure and Regulation of the Rat Somatostatin Gene.- 3. Regulation of Somatostatin Gene Expression by Cyclic AMP.- 4. Peptides Derived from Mammalian Prosomatostatin.- 5. Expression of Preprosomatostatin in Foreign Cells: Secretion of Mature Somatostatin by Yeast (Saccharomyces Cerevisiae).- 6. Cotranslational and Posttranslational Proteolytic Processing of Preprosomatostatin-I and Preprosomatostatin-II in Intact Islet Tissue.- 7. Environmental Regulation of Neurotransmitter Phenotypic Expression in Sympathetic Neurons.- II. Mechanisms of Action.- 8. Side Chain Conformations of Somatostatin Analogs When Bound to Receptors.- 9. Somatostatin Receptor: Evidence for Functional and Structural Heterogeneity.- 10. Structural Analysis of Somatostatin Receptors.- 11. Mode of Action of Somatostatin in Islet B-Cells: Influence on Glucose-, L-isoleucine- and Glyburide-Induced Electrical Activity.- 12. Mechanisms by Which Somatostatin Inhibits Pituitary Hormone Release.- 13. Molecular Mechanisms of Somatostatin Inhibition of. Hormone Release From AtT-20 Cells.- III. Role of Somatostatin in Nervous System Function and Controversies in Somatostatin Research.- 14. Regulation of Hypothalamic Somatostatin Secretion.- 15. Somatostatin and Behavior: Preclinical and Clinical Studies.- 16. Physiological Significance of Somatostatin in Growth Hormone Regulation.- 17. Somatostatin and Depression.- 18. Cytoprotection by Somatostatins.- 19. Evidence for Paracrine Function of Somatostatin.- 20. Evidence for the Endocrine Role of Somatostatin.- IV. Somatostatin in Gastrointestinal Function.- 21. Gut Somatostatin.- 22. Regulation of Somatostatin Release From Dispersed Canine Fundic D-Cells.- 23. Antral Somatostatin: A Paracrine Regulator of Gastrin Secretion.- 24. Somatostatin Inhibits Intestinal Motility Via Modulation of Cyclic Amp-Dependent Cholinergic Transmission ..- 25. Multiple Mechanisms Appear to Underlie the Antisecretory Action of Somatostatin on Acid Secretion.- 26. Somatostatin in Gastrointestinal Function: Intestinal Absorption and Secretion.- 27. Effect of Somatostatin on Exocrine Pancreas.- 28. Somatostatin, Clearance and Inhibition of Gastric Acid Secretion in Duodenal Ulcer Patients.- V. Clinical Applications.- 29. Effect of a Long-Acting Somatostatin Analog (SMS 201-995) on Glucose Homeostasis in Type I Diabetes and in Acromegaly.- 30. Treatment of Diabetes with L363,586.- 31. Somatostatin and Upper Gastrointestinal Hemorrhage.- 32. Somatostatin and Analogs in the Management of Variceal Hemorrhage.- 33. Somatostatin in the Treatment of Hematemesis and Melena.- 34. Somatostatin Octapeptide in the Medical Treatment of Acromegaly.- 35. Efficacy and Safety of a Somatostatin Analogue in Active Acromegaly.- 36. Treatment of Gut-Associated Neuroendocrine Tumors with the Long-Acting Somatostatin Analog, SMS 201-995.- 37. Somatostatin in the Treatment of Acute Pancreatitis.- Author Index.