GASTROINTESTINAL HORMONES
بسم الله الرحمن الرحيم
DIGESTIVE PHYSIOLOGY
II. Hormonal regulation
- Digestive system has its own endocrine system
- It consists of group of special cells called APUD cells (Amine Precursor Uptake and Decarboxylation) present in mucosa of gut
- APUD cells secrete gastrointestinal hormones
- After secretion, the hormones are absorbed and enter portal circulation to liver, through inferior vena cava to the heart and then back to digestive system to exert their actions
APUD cells in mucosa secrete hormones → Absorbed and enter portal circulation → Liver → IVC → Heart →GIT
Secretion of Gastrointestinal Hormones
Regulated by
1. Nervous factors; either through
a) ENS
b) ANS (Sympathetic and parasympathetic)
2. Chemical factors
- These factors affect the APUD cells directly by
a) Blood-borne materials (Carried by blood)
b) Luminal factors (i.e. Factors present in lumen of gut; e.g. Products of digestion, pH, …)
- Gastrointestinal hormones are divided into two main groups or families Family is similarity in structure
a) Gastrin family; Gastrin and cholecystokinine
b) Secretin family; Secretin, Vasoactive Intestinal Polypeptide (VIP) and Glucose-Dependent Insulionotropic Peptide (GIP)
GASTROINTESTINAL HORMONES
A. GASTRIN
i. Introduction
- Polypeptide
- Present in forms of G14, G17 and G34 according to amino acids it contains
- All forms have same C-terminal 5 chain amino acids which is active part of the molecule
- Pentagastrin is a synthetic form and formed of only the active part
- All types of gastrin are inactivated in kidney and small intestine
ii. Sources
a) G cells : Present in mucosa of antrum and duodenal bulb
b) TG cells : Present through the stomach and small intestine
c) Gastrin is present in pituitary gland, hypothalamus and medulla oblongata
iii. Control of secretion
Gastrin secretion is stimulated by
1. Nervous factors
a) Vagal stimulation stimulates gastrin secretion
b) Atropine does not block gastrin secretion
c) Chemical transmitter is not acetylcholine but it is a gastrin releasing polypeptide (GRP) similar to “bombesin”
2. Luminal factors
a) Distention of stomach by food
b) Decreased acidity (Increase in pH) of gastric contents
c) Increase amino acids in gastric contents
Gastrin secretion is inhibited by
1. Luminal factors
a) Increase acidity (Decrease in pH) of gastric contents
2. Blood-borne factors
a) Secretin hormone
b) GIP
c) Somatostatin
iv. Action
1. Increase acidity and pepsin
o Stimulate secretion of HCl and pepsin from glands of stomach
o Negative feedback between acidity and gastrin secretion; Increase acidity decrease gastrin secretion vice versa - Protective mechanism to prevent harmful effect of strong acid on gastric mucosa
2. Stimulates gastric motility
3. Stimulate growth of mucosa of stomach, small and large intestine
B. CHOLECYSTOKININ
i. Introduction
- In the past, it was believed that there were two types of hormones
o CCK stimulates contraction of gallbladder (Cholecyst = Gallbladder/ Kinin = Motility)
o Pancreozymine stimulates exocrine secretion of pancreas rich in enzymes
- Now it’s clear that a single hormone secreted by cells in mucosa of upper small intestine has both activities, called Cholecytokinin-Pancreozymine (CCK-PZ) or most commonly CCK
- CCK present in forms of CCK8, CCK12, CCK33, CCK39 and CCK58
- All the forms have same c-terminal 5 chain amino acids as gastrin (Same family)
ii. Source
- Secreted from I cells in mucosa of upper small intestine (Duodenum and jejunum)
- Found in distal ileum and colon
- Also found in cerebral cortex
- May involved in regulation of food intake
- Related to production of anxiety and analgesia
iii. Control of Secretion
CCK is stimulated by
- Fatty acids and monoglycerides but not triglycerides in duodenum
- Products of protein digestion in duodenum
There’s positive feedback relation between CCK secretion and its stimulation
Increased concentration of fatty acids and products of protein digestion will stimulate secretion of CCK and vice versa
iv. Actions
1. Stimulates contraction of gallbladder, with simultaneous relaxation of sphincter of oddi
2. Stimulates exocrine secretion of pancreas
3. Secrete bicarbonate (HCO3-) from pancreas; Augmenting secretion of secretin
4. Inhibit gastric emptying which important for processes of fat digestion and absorption which require more time
C. SECRETIN
i. Introduction
- Polypeptide contains 27 amino acids
- The whole molecule is needed for activity (If one amino acid is remove, no reaction occur)
- Similar structure to VIP and GIP
ii. Source
- Secreted from S cells located in mucosal glands of upper small intestine
- S cells are stimulated by
o Products of protein digestion
o Acidity of fluid passing from stomach to upper small intestine
iii. Control of Secretion
- Positive feedback relation between secretion of secretin and degree of acidity; Increased acidity stimulate release of secretion hormone
- Secretin stimulates pancreatic exocrine secretion rich in bicarbonate (Alkaline)
- Bicarbonate neutralizes acidity in lumen
- Decreased acidity stops secretion of hormone
iv. Actions
- Stimulates pancreatic exocrine secretion
- Pancreatic secretion is large in volume, watery and rich in bicarbonate
- Bicarbonate causes:
o Neutralization of acidity
o Provides alkaline medium needed for action of pancreatic enzymes
- Action of secretin on pancreas is mediated via cAMP
- Nicotine present in cigarette inhibits secretion of secretin hormone
- No bicarbonate increase acidity - In heavy smokers, there’s hyperacidity which may lead to development of peptic ulcer
D. VIP
Found in
a) Nerves in gastrointestinal tract
b) Brain
c) Autonomic nerves
d) Blood
Secreted as a result of presence of fats in jejunum
Actions:
1. Stimulates secretion of water and electrolytes from intestine; As in diarrhea
2. Inhibits gastric acid secretion
E. GIP
- Polypeptide contains 42 amino acids
- Secreted from K cells present in mucosa of duodenum and jejunum
- Stimulated in response of all three types of nutrients; Glucose, fatty acids and amino acids
Actions
1. Stimulates insulin secretion; Some types of diabetes mellitus is due to hyposecretion of GIP
2. Inhibits gastric acid secretion
Other Gastrointestinal Hormones
F. MOTILIN
- 22 amino acid peptide
- Secreted by cells presents in duodenal mucosa, during fasting states
- Causes contraction of intestinal smooth muscles
- Appears to be a regulator of interdigestive motility that occur at 90 minutes interval, preparing intestine for next meal
G. SOMATOSTATIN The stupidest hormone XDDD
- Growth hormone inhibitory hormone
- Secreted D cells in pancreas and GI mucosa
- Also found in hypothalamus
- Acidity in lumen of upper intestine stimulates its secretion
Actions:
- Inhibits secretion of gastrin, VIP, GIP, secretin and motilin
- Inhibits pancreatic exocrine secretion
- Inhibits gastric acid secretion and motility
Finished this chapter, I can proceed to more interesting topic~ ^-^