Gastrointestinal Hormones Flashcards
Gastrointestinal Hormones — types
GI hormones are broadly divided into three categories:
1) Gastrin family that includes cholecystokinin (cck) and gastrin
2) Secretin family that includes secretin, glucagon, GIP, and VIP
3) Other polypeptides like Motilin, Substance P, Guanylin, Somatostatin
Regulation of GI Function
1) Endocrine regulation: Entero endocrine cell secretes regulatory peptide or hormones that travel via blood stream to remote target organs
example - gastrin, secretin
2) Paracrine Regulation - Regulatory peptide secreted by EEC acts on a nearby target cell by diffusion through interstitial space
EX - Histamine and 5HT
3) Autocrine Regulation - Regulatory peptide secreted by the cells acting on themselves
4) Juxtracrine Regulation
5) Neurocrine Regulation
Gastrin
• Source
- produced by G cells in the stomach that are located mainly in the antral region.
1. G cells of pyloric glands
2. Intestinal G cells in duodenum
3. Islets of pancreas in fetal life.
4. In central nervous system hypothalamus and anterior pituitary
5. Gastrin as a neurotransmitter is also secreted from vagus and sciatic nerve
• Structure
- gastrin is a polypeptide hormone.
- exhibits heterogeneity (have diff polypeptide lengths and diff molecular structures)
Types of gastrins:
1) Depending on the number of amino acids they possess, they are named as G 34, G 17 and G 14
2) Other types of gastrins are C-tetrapeptide (also called as minigastrin) and gastrin containing 45 AA (megagastrin)
3) however, G17 is the principal gastrin secreted from the stomach
• Functions:
- Stimulation of gastric acid and pepsin secretion
- Stimulates the growth of gastric mucosa and mucosa of intestine
- Stimulates gastric Motility
- Stimulates insulin secretion
- causes Contraction of muscles at the gastroesophageal junction. therefore it prevents reflux esophagitis
- causes colonic contraction that initiates gastrocolic reflex after a meal.
- stimulates histamine secretion from ECL
• Mechanism of action
- gastrin acts kn gastrin or cck receptors on parietal cells and increases intracellular calcium concentration via second messenger IP3
- increased cystosolic calcium activates protein kinase that stimulates h+-k+ atpase to promote acid secretion
• Regulation of gastrin
1) Stimuli that increase gastrin secretion:
1. Distension of stomach or duodenum
2. Presence of secretogogues in stomach like caffeine, alcohol, peptones and amino acids which act directly on G cells.
3. Stimulation of vagus.
4. Ca+ rich food.
2) stimuli that decrease gastrin release:
1. High acidic gastric content by negative feedback mechanism (autoregulation of gastrin secretion)
2. Acidic duodenal chyme (Secretes hormones)
3. Intestinal hormones (GIP, VIP, Somatostatin, secretin and glucagon)
Applied:
Gastrinoma - Gastrin-secretinh tumour causes severe and chronic hypergastrinemia that causes peptic ulcer disease which is often refractory and severe. this is called Zollinger-Ellison Syndrome.
Gastrin secretion is also elevated in pernicious anemia, in which the acid secretion in the stomach is less as the parietal cells are damaged. this causes feedback release of gastrin from g cells.
Cholecystokinin
• Source -
Secreted from I cells in the mucosa of upper small intestine.
1. Hypothalamus.
2. Peripheral nerves. (of distal ileum and colon)
3. Cerebral cortex.
• Structure
- polypeptide hormone
1. there are different forms of cck depending on the number of amino acids present like CCK 58, CCK 39, CCK 33, CCK 12, CCK 8, CCK 4
2. cck secreted from duodenum and jejunum are usually cck 12 and cck 8
cck in the enteric and pancreatic nerves is mainly cck 4.
the forms of cck in the brain are primarily cck 58 and cck 8
• Functions
- causes contraction of gall bladder therefore cck increases the bile release into the intestin
- stimulates pancreatic secretion rich in enzymes. therefore cck is also called as Cholecystokinin-Pancreozymin (CCK-PZ)
- augments the action of secretin
- causes relaxation of sphincter of oddi
- stimulates colonic movements
- prevents reflux of duodenal contents into the stomach
- inhibits gastric acid secretion
- inhibits gastric Motility, thereby delays gastric emptying.
- Causes inhibition of feeding centre in hypothalamus and limits food intake.
Mechanism of Action:
- two cck receptors - CCK A and CCK B
- CCK A receptors are mainly located in the peripheral structures like gallbladder, pancreas, GI tract etc
- CCK B receptors are present in central structures like brain areas
- CCK acting on both receptors activates membrane phospholipase C and stimulates production of intracellular IP3 and DAG
Regulation of secretion:
Factors that increase CCK secretion
1. contact of intestinal mucosa with products of digestion especially fatty acids, peptides and amino acids
2. bile and pancreatic juice facilitate digestion of protein and fat. therefore, they provide positive feedback for cck secretion
Secretin
- First hormone to be discovered (Bayliss and Starling)
• Source
- Secreted from S cells located in the mucosa of upper part small intestine
- Neurons in limbic system.
• Structure
- Polypeptide hormone containing 27 Amino acids
• Functions
- increases secretion of pancreatic juice rich in bicarbonate (watery and alkaline pancreatic secretion)
- also increases alkaline bile secretion
- augments the action of cck to produce pancreatic secretion rich in enzymes
- decreases gastric acid secretion and Motility
- causes contraction of pyloric sphincter
• Mechanism of Action
- Secretin acts on adenylate cyclase on the cell membrane and increases cytosolic formation of cAMP
• Regulation of Secretion
- secretion of secretin is increased by acidic chyme and products of protein digestion entering the upper part of intestine
- the increased ph of duodenal and upper jejunal content decreases secretin secretion by feedback mechanism
Gastrin Inhibitory Peptide
• Source
- by k cells present in mucosa od duodenum and jejunum
• Structure
- Glucose dependent insulinotropic polypeptide (GIP) is a polypeptide hormone containing 42 amino acids.
• Functions
- inhibits gastric secretion and Motility
- stimulates insulin secretion
• Regulation
Secretion of GIP is increased by glucose and fat in the stomach and duodenum
Substance P
- Secreted from endocrine cells and neurons of entire GIT starting from stomach to colon.
- It increases intestinal motility.
Motilin
- Causes contraction of intestinal smooth muscles and therefore, increased GI Motility, esp in the interdigestive phase
- major regulator of migrating motor complex (MMC)
- secretion of motilin is dec following the ingestion of food and remains low until the digestion of food is complete. then the conc increases and activates MMC that sweeps and cleans the intestine. Thus, it prepares the intestine for next meal
