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22 Cards in this Set
- Front
- Back
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GI Hormone biologically active form
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Most GI hormones are produced in "pre-pro" form.
Must be activated |
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Site of production of major hormones: Gastrin, CCK, secretin, GIP, motilin
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Gastrin
-Antrum -Duodenum CCK -Duodenum -Jejunum -Ileum Secretin -Duodenum GIP -Duodenum -Jejunum Motilin -Duodenum -Jejunum |
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Gastrin family: structure and receptor binding
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Homology at the last five amino acids (pentagastrin).
Sulfated tyrosyl residue at the COOH end - 6th from the end in gastrin, and 7th in CCK Gastrin’s biological activity resides in the last four amino acids Gastrin binds to the CCK-B receptor now known as CCK-2 The sulfate group does not affect gastrin’s affinity. CCK binds CCK-A now CCK-1 receptor and with less affinity to CCK-2 The sulfate group on tyrosine 7 gives CCK the selectivity for CCK-1 receptors. CCK with no sulfate on the tyrosine behaves like gastrin. For the short peptide CCK-8 the presence of the sulfate group does not provide receptor selectivity with a similar Ki for both CCK1 and CCK2 |
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Gastrin effects: acid production
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Acid secretion
-Amidated form -Gastrin (from G-cell) directly stimulates parietal cells to secrete HCl into stomach -Gastrin stimulates ECL cell which secretes histamine that stimulates parietal cell to secrete HCl -Gastrin stimulates D-cell which produces somatostatin which inhibits parietal cell, G-cell, and ECL cell |
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Gastrin effects: cell proliferation
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Both amidated and glycine extended forms
On different cell types with CCK2R -Parietal cells, ECL cells |
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Regulation of gastrin secretion
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Stimulatory:
-Gastric distention has a positive vagal effect which has a positive effect on enteric neurons, releasing gastric releasing peptide (GRP) which has a positive effect on the G-cell -Amino acids directly stimulate the G-cell Inhibition: -Acid secretion stimulates D-cell which produces somatostatin which inhibits G-cell |
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CCK: functions
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Stimulates bile secretion
Stimulates pancreatic enzymes and pancreatic growth Inhibits gastric emptying Activates vagal afferent fibers -Signal returns as an efferent vagal stimulation to pancreatic secretion and inhibition of gastric emptying |
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Secretin: function
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Stimulates pancreatic fluid secretion (rich in bicarbonate)
Stimulates pancreatic growth Stimulates hepatic HCO3 secretion Inhibits gastric acid secretion -Is released if duodenal pH<4.5 or if there are fatty acids |
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Incretin hormones: cells, function, breakdown, diabetes
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GLP-1 (Glucagon like peptide 1)
-L cells -controlled by neural and endocrine factors rather than direct nutrient stimulation GIP (Gastric inhibitory peptide or glucose-dependent insulinotropic polypeptide) -K cells Hormones that can explain incretin effect (stimulate insulin secretion) -Augmentation is 3 to 4 fold GIP and GLP-1 also inhibit glucagon secretion and decrease gastric emptying. GIP seems to be more important regarding insulin secretion. GLP-1 is a more potent agonist, thus a better candidate as a potential drug Broken down by DPP-4, which stops incretin effect -DDP-4 inhibitors (januvia) treat type 2 diabetes GLP-1 analog (Byetta) controls type 2 diabetes |
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Incretin hormones: mechanism
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Receptor in pancreatic cell
cAMP Ultimate outcome is release of insulin |
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GIP: release
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AA, fatty acids, and glucose stimulate release of GIP from K cells in duodenum
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Motilin
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Affects intrameal (fasting) motility through contractility
Responsible for MMC (migratory motor complex) |
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Hormones affecting appetite: cells, effect
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PYY
-Synthesized in L cells in colon -Reduces food intake Ghrelin - Synthesized in X (A-like) endocrine cells in stomach -Increases food intake Leptin - Synthesized in adipocytes |
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PYY
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36 AA peptide
Member of the NPY family Binds the Y2 receptor type Secretion suppressed by fasting (reduces food intake) Induces sensation of satiety |
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Ghrelin
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Ghrelin
28 AA peptide Related to motilin Binds the GHS-R receptor Secretion stimulated sharply before a meal and suppressed by meal ingestion Induces sensation of hunger Also has effects on contractility |
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Physiologic modulators of gastrin, CCK, secretin, GIP/GLP-1, motilin, PYY, ghrelin
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Gastrin
-Stimulated by protein, distension, and neural -Inhibited by acid CCK -Stimulated by protein, fat, and acid Secretin -Stimulated by fat and acid GIP/GLP-1 -Stimulated by protein, fat, and sugars Motilin -Stimulated by fat, acid, and neural PYY -Stimulated by fat, sugars, and neural Ghrelin -Stimulated by neural |
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Physiologic action of gastrin, CKK, secretin, GIP/GLP-1, motilin, PYY, ghrelin
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Gastrin
-Stimulates acid secretion -Gastric cell proliferation CCK -Inhibits gastric emptying -Stimulates pancreatic HCO3, pancreatic enzymes, gall bladder -Pancreatic cell proliferation Secretin -Inhibits acid secretion -Stimulates pancreatic HCO3, bile HCO3 -Pancreatic cell proliferation GIP/GLP-1 -Inhibits gastric motlility -Stimulates metabolic effect Motilin -Stimulates gastric and intestinal motility PYY -Decreases metabolic effect Ghrelin -Stimulates metabolic effect |
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GI paracrine factors
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Somatostatin
Histamine Serotonin Nitric oxide VIP Gastrin releasing peptide |
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Somatostatin
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Gastrin, acid, or fat stimulates D-cell
Somatostatin released and will diffuse locally to inhibit gastrin secretion |
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Histamine
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ECL has gastrin receptor (CCKR2) which activates it and stimulates secretion of histamine
Also stimulated by ACh Histamine released and acts locally -Stored in vesicles where it is incorporated by VMAT2. Release is a Ca activated process requiring docking of secretory vesicle to SNARE membrane protein -Stimulates acid secretion |
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Serotonin
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Concentrated in enterochromaffin cell
Enterochromaffin cell has direct contact with lumen Mechanical distention and a variety of neurohormonal stimuli releases serotonin which acts locally to regulate intestinal fluid transport and peristalsis Plays an important role in reflexes and might have role in IBD |
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Nitric oxide
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Acts as important mediator of nonadrenergic, noncholinergic inhibitory innervation of intestinal smooth muscle and/or ICC
Neuromodulator Altered expression linked to achalasia, diabetic gastroparesis, hypertrophic pyloric stenosis |
