GIT HORMONES
GIT is regarded as the largest endocrine organ in the body. Collectively, GIT hormones influence motility, secretion, digestion, and absorption in the gut. In addition, they regulate bile flow, secretion of pancreatic hormones, affect tonicity of vascular walls, blood pressure and cardiac output. The principle GIT hormones include: - Gastrin - secretin - cholecystokinin- pancreozymin (cck- pz) - vocative intestinal polypeptide (VIP) - Gastric inhibitory polypeptide (GIP) - othersGastrin There are 3 molecular forms of gastrin that are present in the blood circulation and the tissues and these are: 1. Big Gastrin; which is a linear polypeptide of 34 amino acids called as (G- 34). 2. Little gastrin; which is a linear polypeptide of 17amino acids called as (G- 17). 3. Minigastrin; which is a linear polypeptide of 14 amino acids called as (G- 14). However, they all exert the same biological effects on the target cells. Gastrin is secreted and stored by endocrine cells called as (G cells) mainly in the antral mucosa of the stomach, and to a lesser extent by G cells of the proximal part of the duodenum, and by (D- cells) of the pancreas. Following secretion to the blood stream, the main circulating form is (G- 34). Gastrin has the following main functions:
1.Stimulates the fundal parietal cells to secrete the gastric acid. 2. Stimulates gastric mucosal cells to secrete pepsinogen and intrinsic factor. 3. Stimulates small intestinal mucosal cells to secrete a hormone called (secretin). 4. Stimulates the secretion of pancreatic enzymes and bicarbonate (HCO3-). 5. Stimulates gastric and intestinal motility. 6. Stimulates gastric mucosal growth. 7. Stimulates hepatic bile flow.
The main stimulus for the release of gastrin is antral dilatation due to presence of food in the stomach mainly protein digestion products (polypeptides, peptides, and amino acids). In addition, other stimuli may include: - alcohol - caffeine - insulin induced hypoglycemia - vagal stimulation (sight, smell, taste, thinking) Maximum secretion of gastrin occurs at an antral Ph of 5-7. However, when pH gets lower a negative feed back mechanism will inhibit further secretion of gastrin.
Cholecystokinin- Pancreozymin It is a (33) a.a. polypeptide hormone released from the upper small intestinal mucosal cells (I cells) mainly in the duodenum in response to: presence of partially digested protein products in the lumen of the intestine. entry of gastric acid to the intestine. Presence of fatty acids mainly in the form of micells. As the name implies, it stimulates the gall bladder contraction, and meanwhile the secretion of pancreatic enzymes. It is present in multiple molecular forms; the most active form is that containing the sulfated tyrosyl residue. The five a.a. sequence at the C- terminal end are identical to those of gastrin.
The structural similarity with gastrin makes CCK- PZ exerts some gastric action mainly in stimulating intestinal motility and increasing pancreatic enzymes. It competes with gastrin for its intestinal receptors and this may help in terminating gastrin action following meals.
Secretin It is a polypeptide with structural similarity VIP, GIP and Glucagon. It is released from the granular mucosal cells (S- cells) that are mainly present in the duodenum, but however are distributed throughout the small intestine. It is called as such because it permits the good flow of pancreatic juice following meals. Secretin release is stimulated by contact of S- cells with gastric acid. However, its only inhibitor is somatostatin. The principle function of secretin is increasing pancreatic juice release with increased concentration of bicarbonate. So, it is used for testing pancreatic function. It inhibits gastrin release and thus gastric acid secretion.
Vasoactive Intestinal Polypeptide (VIP) It is a linear polypeptide of 28 a.a., has some structural similarities with secretin, GIP, and Glucagone. It is present in almost all body tissues, but mainly concentrated in the GIT and the nervous system. It is present in the nerve fibers along all of the gut from the esophagus to the colon, but mainly in the jejunum, ileum, and the colon. VIP has a large no. of ill defined non- specific physiological effects, among which are: 1. Acts as a neurotransmitter in the CNS and in the autonomic nervous system of the gut. 2. Relaxation of the smooth muscle fibers in vessels walls, gut, and genito- urinary system. 3. Increases pancreatic secretion. 4. Increases water and electrolytes secretion from the gut. 5. Inhibition of gastrin release and thus gastric acid secretion. 6. Increases hormonal release from the pancreas, gut, and hypothalamus. 7. Stimulation of lipless, glycogenolysis, and bile flow.
Gastric Inhibitory Polypeptide (GIP) It is consisted of 42 a.a. released from [K- cells] which are located in the jeujenal and duodenal mucosa. Its main functions include: 1. In the presence of hyperglycemia, like following meals, it stimulates the secretion of insulin. This is the most important action of GIP, and that is why it is called {Glucose dependant insulinotropic peptide}. 2. Decreases intestinal motility despite increased intestinal secretion of water and electrolyte. 3. In supraphysiological concentrations, it acts to inhibit gastric acid, pepsin, and gastric secretion.
Other Hormones of the Gut Other hormones of the gut include: Somatostatin: It is one of the most potent well known inhibitory hormones for a lot of endocrine secretion. It inhibits the release (as well as the action on the target cells) of a lot of hormones including gastrin, secretin, GIP, insulin, glucagon, VIP, pancreatic polypeptide, and others. Motilin: It acts to increase the contraction of the smooth muscle fibers in the upper GIT namely the lower esophageal sphincter, gastric fundus, antrum, and duodenum. Its unique feature is that its actions are restricted to fasting state only.
Pancreatic Polypeptide (PP): It is mainly secreted from the pancreas. It acts to increase and then decrease (i.e. biphasic action) the pancreatic secretion of water, electrolytes, and enzymes. Its high blood levels can be used as a landmark of pancreatic endocrine tumors. Enteroglucagon: Is a group of substances that are released from the gut but have biological effects similar to pancreatic glucagon (i.e. catabolic hyperglycemic) although are chemically different.