Gastrointestinal hormones |Gastrin| Secretin |

                                                    GIT Hormones

Introduction: In this article, we will learn about different hormones secreted by the gastrointestinal tract, their secretion, mode of secretion, and functions.

Keywords: CCK- PZ | VIP | Secretin | GIP | Ghrelin | Motilin | Neurotensin| Substance P| Peptide Y.Y.| Somatostatin |APUD|Gastrin|Human physiology| Self study

Table of contents

1.	Introduction
2.	Classification
3.	Mechanism of secretion
4.	Mechanism of action
5.	Regulation of secretion
6.	Functions

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Gastrointestinal hormones are biologically active polypeptides secreted from the endocrine cells of the GIT mucosa. These hormones go into the portal circulation, then into the systemic circulation, and then to the target tissue. Some gastrointestinal hormones also function as paracrine and autocrine hormones to regulate G.I. functions. They are chemical messengers. 

In physiological amounts, they perform specific functions, but at a high level, their actions overlap. They are directly exposed to GIT content. The chemicals present in the food or digested food products influence their secretion. They regulate the secretion, digestion, absorption, and motility of GIT. They also act as neurotransmitters and neuromodulators.

Enteroendocrine cells are endocrine cells present in the GIT mucosa. They do not form glands and are widely distributed in the digestive tract, stomach, and small intestine pancreas. There are more than 50 GIT hormones or gut hormones that make the gut the body's largest endocrine organ.  

Neuroendocrine cells are endocrine cells present in other organs. They are APUD (amine precursor uptake and decarboxylation .)

Classification of GIT Hormones

Types of gastrointestinal hormones are grouped into three groups based on their chemical structure:

1. Gastrin family.

2. Secretin family and

3. Other GIT hormones.

                                                Gastrin family

Gastrin was first discovered by Edkins in 1906, and almost 55 years later, Gregory and Tracy isolated the pure forms of gastrin. 

It is mainly secreted by gastrin G cells in the gastric mucosa's deeper portion of pyloric glands. The cells are flask-shaped, apex projecting toward the lumen, and contain many microvilli with many granules of gastrin. The microvilli have many receptors for chemicals.

Other sites: G cells are APUD cells and are present in the Pituitary gland, Hypothalamus, and Medulla oblongata. Gastrin is also secreted from the vagus and sciatic nerve as neurotransmitters.

It is secreted as Progastrin, which is converted into gastrin by HCL and is a product of digestion. Gastrin occurs in 3 primary forms –G-34, G-17, and G-14, containing  34,17,14  amino acids, respectively .G-17 is also known as little gastrin and is the main form of gastrin released after a meal and is removed rapidly from the circulation. .G-34 is present during fasting. 

Other types are- Minigastrin-C-tetra polypeptide.

                                Megagastrin- has 45 aminoacids.

Gastrin enters the general circulation –inactivated in the intestine and degraded in the kidney. Its half-life is 2-3 minutes. Progastrin is synthetic gastrin.

Mechanism of action: Gastrin acts on gastrin and CCK receptors on the parietal

cells, causing an increase in intracellular Ca⁺⁺ via second messenger IP₃. Increased cytosolic calcium activates protein kinase that stimulates H⁺K⁺ ATPase, increasing acid secretion.

Factors influencing   gastrin secretion:

Factors increasing   gastrin secretion:

1. Peptide and amino acids in the stomach.

2. Distension of pyloric antrum acts by the local enteric nervous system.

3. Increased vagal discharge mediated via gastrin-releasing peptide (GRP) or Bombesin.

4. Ca⁺⁺ ions.

Factors decreasing  gastrin secretion:

1. Acid in the antrum inhibits gastrin secretion by direct action and somatostatin. This is a negative feedback effect of acid.

2. Secretin , VIP ,GIP ,Glucagen ,calcitonin etc.

Functions:

1. Stimulates secretion of gastric acid.

2. Stimulates secretion of pepsin.

3. Stimulates secretion of histamine from enterochromaffin-like cells (ECL)

4. Stimulates gastric motility and causes contraction of the lower oesophageal sphincter.

5. Stimulates contraction of the gall bladder.

6. Stimulates secretion of insulin, glucagon, and secretin.         

7. Stimulates proliferation and differentiation of stomach epithelium, small and large intestine. Therefore, it may be involved in atrophy or neoplasm of GIT mucosa.

Clinical: Gastrinoma is a gastrin-producing tumor that may originate in the stomach, duodenum, or pancreatic δ cells-  Zollinger Ellison syndrome -is the most common - in these cases, a large amount of gastrin is secreted, causing increased HCl production and peptic ulcer.

                                                            CCK-PZ

Cholecystokinin-pancreozymin is a polypeptide produced by I cells in the mucosa of the duodenum, jejunum, and upper portion of the ileum. It is also found in neurons in the brain- cerebral cortex-somatic nerves and nerves of the distal ileum and caecum.

Types: Depending on the number of amino acids, CCK-PZ has many types: CCK-PZ-4.8,12,33, and many others.

Half-life is 5 minutes.

Mechanism of action: CCK-PZ acts on CCK-PZ  A and CCK-PZ  B receptors.

CCK-PZ   A is mainly located in peripheral organs like G.B., GIT, and Pancreas.

CCK-PZ   B is present in the brain.

When attached to these receptors, it activates Phospholipase C and stimulates the production of Intracellular IP₃ and DAG, causing an increased flow of pancreatic juice rich in enzymes.

Functions:

1. Increases contraction of the gall bladder. So, it increases the release of bile and relaxes the sphincter of Oddi.

2. Increases secretion of pancreatic juice rich in enzymes.

3. Stimulates the action of secretin to produce alkaline juice by the pancreas.  

4. Decreases secretion of gastric acid.

5. Decreases gastric motility.

6. Increases motility of small intestine and colic movements.

7. Stimulates secretion of glucagon.                             

8. Stimulates cell formation of pancreas trophic effect.

9. Increases secretion of enterokinase from the duodenum.

10. In the brain, it is anorexigenic.

Factors influencing CCK-PZ  secretion:

Factors increasing  CCK-PZ  secretion:

The acids in the duodenum are fatty acids, peptides, and amino acids.

There is positive feedback –a product of digestion stimulates increased CCK-PZ  secretion and increases bile and pancreatic juice rich in enzyme secretion, which will cause more digestion. This is terminated when the outcome of digestion enters the ileum.

.Factors decreasing  CCK-PZ  secretion decrease when the product of digestion enters the ileum.

                                                Secretin

 Secretin is the first hormone discovered by  Bayliss and Starling in 1902. Secretin is secreted by S cells in the crypts of the mucosa's upper part of the small intestine, duodenum, and jejunum. It is secreted as a proenzyme called prosecretin, which is converted into active secretin by gastric acid and salts of fatty acids. After secretion, it is liberated into the portal venous blood and, via systemic circulation, reaches pancreatic tissue to exert effects.

Structure: It is a polypeptide with 27 amino acids. Its structure resembles that of a VIP.GIP, Glucagon.

Mechanism of action: Pancreatic centro acinar cells have secretin receptors in their plasma membrane. When secretin binds to these receptors, it stimulates adenyl cyclase activity and converts ATP to c-AMP in the pancreatic duct cells. c-AMP acts as the second messenger in intracellular signal transduction, producing alkaline watery pancreatic juice secretion and poor enzymes. Meanwhile, CCK-PZ  causes an increased flow of pancreatic juice rich in enzymes.

Secretin also increases water and bicarbonate from duodenal Brunner's glands. In addition, it modulates water and electrolyte transport in pancreatic duct cells, liver cholangiocytes, and epididymis epithelial cells. It also plays a role in the vasopressin–independent regulation of renal water reabsorption.

Secretin is also present in the magnocellular neurons of the paraventricular and supraoptic nuclei of the Hypothalamus and the neurohypophysis. In addition, it is released from the posterior pituitary during increased osmolality.

The Hypothalamus activates vasopressin release. It is also essential for the significant effect of angiotensin II.

Secretin and its receptors are present in discrete nuclei of the Hypothalamus, including the paraventricular and arcuate nucleus, which are the primary brain sites for regulating body energy homeostasis.

 When the volume of pancreatic juice increases, its Cl- concentration falls, and HCO3- concentration rises. HCO3- is secreted in small pancreatic ducts but reabsorbed in the large pancreatic ducts in exchange for Cl-.

Functions:

1. Increases secretion of pancreatic juice rich in bicarbonate –watery and alkaline pancreatic juice.

2. Stimulates the action of   CCK-PZ  to produce enzyme-rich juice by the pancreas.  

3. Decreases secretion of gastric acid.

4 . Increases contraction of the pyloric sphincter. So, it delays gastric emptying. 

5. Stimulates alkaline bile secretion.

Factors influencing  secretin secretion:

 Acidic chyme and products of protein digestion-peptide and amino acids increase its secretion.

The alkaline content of the duodenum and upper jejunum decreases its secretion.

                       

                                 Gastric Inhibitory Polypeptide    GIP

It is also known as Glucose-dependent insulinotropic polypeptide. It is produced by K cells present in the duodenum and upper jejunum mucosa.

Its secretion is stimulated by glucose and fat in the duodenum and upper jejunum.

Functions:

1..Decreases secretion of gastric acid.

2. Decreases gastric motility.

3. Stimulates β cells of the pancreas to increase secretion of insulin.

                                 Vasoactive intestinal peptide VIP

It is present in the GIT released from jejunum in response to fatty meals. It is also present in the blood, the brain, and ANS.

Functions:

1. Relaxes intestinal smooth muscle of the gut, including sphincters, blood vessels, and genitourinary system.

2. Decreases gastric motility.

3. Stimulates secretion of electrolytes and water.

4. Increases the action of A-ch on salivary glands, causing profuse secretion of watery saliva with a relatively low content of organic material and protein.

5. Peripheral blood vessels dilate.

Glucagon :

Glucagon secreted by the gastric and duodenal mucosa is different from glucagon secreted by α cells of islets of  Langerhans –pancreas.

Functions: it reduces glucose levels in hyperglycemia.

Principle gut regulatory peptides are Gastrin, CCK-PZ, Secretin, and VIP.

                                    Other GIT Hormones

Motilin: secreted by Mo cells in the stomach, duodenal, and colon mucosa. Regulates intestinal motility by causing contraction of intestinal smooth muscles.

Neurotensin: secreted by mucosal cells of the ileum in response to fatty acids.

It inhibits GIT motility.

Peptide Y.Y.: secreted by mucosal cells of the jejunum in response to fatty diets.

It inhibits GIT motility and gastric acid secretion.

Substance P is found in the endocrine cells and nerve cells in the GIT.

Causes increased motility.

GRP =Gastrin releasing peptide from vagus nerve ending of G cells. Causing increased gastric secretion. 

Ghrelin: a peptide hormone from the stomach and liver. This is often known as the Hunger hormone due to its high level being detected in fasting individuals. Ghrelin agonists are being used to treat anorexia and loss of appetite.

 Amylin controls glucose levels and gastric motility.

Oxyntomodulin controls acid secretion.

Somatostatin:=Growth hormone inhibiting hormone ( GHIH)- is produced by δ cells of islets of Langerhans –pancreas and GIT mucosa.

It is an inhibitory hormone and inhibits the secretion of Gastrin, VIP, GIP, Secretin, motilin, insulin, glucagon, pancreatic juice, and gastric acid secretion.

It inhibits GIT motility and contraction of G.B.

It inhibits the absorption of glucose, fatty acids, and amino acids.

(GRP =Gastrin releasing peptide, Somatostatin:=Growth hormone inhibiting hormone-GHIH)

 

	Name of Hormone	secreted by	Functions
1.	Motilin	Mo cells in the mucosa of the colon stomach duodenum	Regulates intestinal motility.
2.	Neurotensin	Mucosal cells of the ileum  response to fatty acids	Inhibits GIT motility
3.	Peptide Y.Y.	Mucosal cells of the jejunum respond to fatty foods.	Inhibits GIT motility & gastric acid secretion
4.	Substance P	Endocrine and nerve cells in the GIT.	Increased motility
5.	GRP	From the vagus nerve ending of G cells	Increased gastric secretion
6.	Somatostatin	δ cells in the islets of Langerhans of the pancreas and GIT mucosa.	Inhibits gastrin, VIP, GIP Secretin, motilin, insulin, Glucagon, and Gastric acid pancreatic juice inhibit the motility of GIT, contraction of GB, and absorption of A.A., F.A., and glucose.

 

 Hashtags: Gastrin # CCK-PZ # VIP # Secretin # GIP # Ghrelin # Motilin # Neurotensin # Substance P # Peptide Y.Y.# Somatostatin #APUD

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1 salivary glands -we must know glands

2. https://blog.totalphysiology.com/2021/06/gastrointestinal-tract-introduction.html

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