Gastrin: A Gastrointestinal Hormone

Gastrin: A Gastrointestinal Hormone

Keywords:

Paracrine|Endocrine|Autocrine|pancreatic δ cells|Zollinger-Ellison syndrome| Health|Medical topic

Table of Contents

1. Gastrin: A Gastrointestinal Hormone
   1. Keywords:
   2. Table of Contents
   3. Introduction:
2.  Gastrin family
   1. Forms of Gastrin:
   2. Mechanism of Action: 
   3. Factors influencing   gastrin secretion:
      1. Factors increasing   gastrin secretion:
      2. Factors decreasing  gastrin secretion:
   4. Functions:
   5. Clinical: 

Introduction:

Gastrointestinal hormones are biologically active polypeptides secreted from the endocrine cells of the gastrointestinal mucosa. These hormones enter the portal circulation, then flow into the systemic circulation, and finally reach the target tissue. Some gastrointestinal hormones also function as paracrine and autocrine hormones to regulate gastrointestinal (GI) 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 the GIT content. The chemicals present in the food or digested food products influence their secretion. They regulate the secretion, digestion, absorption, and motility of the 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 throughout the digestive tract, including the stomach, small intestine, and pancreas. There are more than 50 gut hormones, collectively referred to as GIT hormones, that make the gut the body’s largest endocrine organ.  

Neuroendocrine cells are a type of endocrine cell found in various organs. They are APUD (amine precursor uptake and decarboxylation).

Types

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, with the apex projecting toward the lumen, and contain numerous microvilli and many granules of gastrin. The microvilli have many receptors for chemicals.

Other sites: G cells are APUD cells and are found in the Pituitary gland, hypothalamus, and medulla oblongata. Gastrin is also secreted from the vagus and sciatic nerve as a neurotransmitter.

It is secreted as Progastrin, which is converted into gastrin by HCL and is a product of digestion. 

Forms of Gastrin:

Gastrin occurs in three primary forms – G-34, G-17, and G-14, containing 34, 17, and 14 amino acids, respectively. G-17 is also known as little gastrin and is the primary form of gastrin released after a meal, which is then rapidly removed from the circulation. G-34 is present during fasting. 

Other types are- Minigastrin-C-tetra polypeptide.

                                Megagastrin has 45 amino acids.

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

Mechanism of Action: 

Gastrin acts on the gastrin and CCK receptors on the parietal cells, causing an increase in intracellular Ca⁺⁺ via the 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. Peptides and amino acids in the stomach.

2. Distension of the pyloric antrum is acted on 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 an adverse feedback effect of acid.

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

Functions:

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

Clinical: 

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

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