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Transcript
Hormones of the Gut I. Beginning of Endocrinology A. Bayliss and Starling--1902 1. Acidification of denervated duodenum or jejunum stimulated pancreatic exocrine secretion. 2. Injected extract of jejunal mucosa also stimulated pancreatic exocrine secretion. 3. Postulated a humoral regulatory factor they called “Secretin.” B. Secretin finally isolated in 1961. II. Gut Regulatory Peptides A. Gut Nervous System B. Endocrine cells of mucosa 1. Basal secretory granules C. Gut Peptides may be 1. Hormones a) Travel to different organ through blood stream. 2. Paracrine 3. Neurosecretory 4. Neurotransmitters III. Secretin A. 29 amino acid peptide 1. Related to: glucagon, GIP, VIP, PHI, PHM (Secretin family) B. Action: 1. Stimulates Bicarbonate and Water Secretion by Pancreas C. Secretin Control IV. Gastrin A. 1905, Edkins discovered that an extract of gastric mucosa stimulated acid secretion that he called Gastrin. B. 1960s, Gregory isolated and sequenced Gastrin. C. 3 biologically active forms: 1. “Big” = 34 amino acids 2. ‘Little” = 17 amino acids 3. “Mini” = 14 amino acids 4. Structurally similar to Cholecystokinin: a) Gastrin-Cholecystokinin Family. D. Found in endocrine cells of gastric antrum. 1. Also identified in CNS. E. Stimulated by proteins and amino acids in gastric lumen. 1. Carbohydrates and Fats in effective. 2. Somatostatin inhibits Gastrin release F. Gastrin Action 1. Stimulates Acid Secretion by Gastric Mucosa a) May be due to stimulation of histamine release by neighboring cells (paracrine) 2. Stimulates growth of parietal cells of the Gastric Mucosa 3. Stimulates Mucosal blood flow 4. Stimulates Pepsin Release G. Gastrin Control V. Cholecystokinin (CCK) A. History 1. 1928: Fat in small intestine stimulates the gall bladder to contract--cholecystokinin. 2. 1940s: Extract of duodenal mucosa stimulates pancreas to secrete enzymes--pancreozymin. 3. 1964-8: Purification of a single substance that stimulated both contraction of the gall bladder and pancreatic enzyme secretion--settled on one name: cholecystokinin (CCK). B. Structure 1. Polypeptide found in different forms including: 58, 39, 33, & 8 amino acids. 2. 8 amino acid form has full biological potency. 3. Carboxy terminal 8 amino acids identical in all forms. 4. Larger forms may be prohormones. 5. Preprocholecystokinin found: 115 amino acids. C. Cholecystokinin Location: 1. Located in duodenal and proximal jejunal mucosa. 2. Also found in CNS. D. CCK Secretion Stimulated 1. By the presence of intraduodenal protein or fat. 2. May be a low molecular weight CCK-releasing factor. 3. Release is inhibited by somatostatin. E. CCK Actions 1. Stimulates contraction of gall bladder, forcing bile into the duodenum. 2. Stimulates pancreatic enzyme secretion. 3. Trophic effects on pancreatic acini. 4. Causes sphincter of Oddi to relax. 5. Induces satiety. F. CCK Control VI. Somatostatin A. 14 & 28 amino acid forms. B. Found in hypothalamus, throughout CNS and Gut (including pancreas) C. Major inhibitory peptide of Gut. Inhibits secretion of 1. insulin 2. glucagon 3. CCK 4. secretin 5. gastrin 6. VIP 7. somatostatin (autocrine) D. Somatostatin Control VII. Other Peptides A. Vasoactive Intestinal Peptide (VIP) 1. Neurotransmitter/neuroendocrine 2. Relax esophageal and anal sphincter 3. Increases blood flow in the gut 4. Causes penile erection B. Gastrin-Releasing Peptide (GRP) 1. Neurotransmitter/neuroendocrine 2. Stimulates release of Gastrin C. Substance P 1. Neurotransmitter 2. Stimulates Contraction of Smooth Muscle D. Enkephalins E. Neurotransmitter F. Inhibits gut motility, antagonizes action of Substance P