Which of the following does not affect gastric acid secretion: acetylcholine (ACh) stimulating via muscarinic receptors, bisphosphonates, calcium antagonists inhibiting, hydrogen ion release via H'+K'+ATPase, or theophylline?

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Gastric Acid Secretion: Identifying the False Statement

Bisphosphonates stimulate gastric secretion is FALSE. Bisphosphonates do not stimulate gastric acid secretion; in fact, they can cause gastric irritation and damage.

Examination of Each Statement

1. Acetylcholine stimulates gastric acid via muscarinic receptors

This statement is TRUE. Acetylcholine is a key neurotransmitter in the regulation of gastric acid secretion that works through muscarinic receptors on the parietal cell. According to research evidence, acetylcholine stimulates gastric acid secretion via an increase in cytosolic calcium 1, 2. The muscarinic receptors on parietal cells have been identified as M3 subtype 1.

2. Bisphosphonates stimulate gastric secretion

This statement is FALSE. Bisphosphonates do not stimulate gastric acid secretion. On the contrary, bisphosphonates are associated with gastric irritation and damage. According to research evidence, bisphosphonates have been linked to gastrointestinal intolerance and can induce gastric damage 3. They are primarily used for bone diseases and have no role in stimulating gastric acid production.

3. Calcium antagonists inhibit gastric acid secretion

This statement is TRUE. Calcium antagonists (calcium channel blockers) inhibit gastric acid secretion by interfering with the calcium-mediated pathway. Since the stimulatory effect of acetylcholine and gastrin on gastric acid secretion is mediated via an increase in cytosolic calcium 1, 2, calcium antagonists that block this pathway would inhibit gastric acid secretion.

4. Hydrogen ion is released via H+K+ ATPase

This statement is TRUE. The H+K+ ATPase (proton pump) is the final common pathway for acid secretion in the parietal cell. This enzyme is responsible for the exchange of hydrogen ions for potassium ions across the parietal cell membrane, resulting in the secretion of hydrochloric acid into the gastric lumen 1, 2. Proton pump inhibitors work by inhibiting this enzyme.

5. Theophylline stimulates gastric acid secretion

This statement is TRUE. Theophylline is a methylxanthine that inhibits phosphodiesterase, leading to increased levels of cyclic AMP. Since histamine stimulates gastric acid secretion through the activation of adenylate cyclase and generation of cAMP 1, 2, theophylline can potentiate this pathway and stimulate gastric acid secretion.

Mechanisms of Gastric Acid Secretion

Gastric acid secretion is regulated by a complex interplay of:

  1. Neural mechanisms: Acetylcholine from vagal stimulation acts on M3 muscarinic receptors on parietal cells, increasing cytosolic calcium and stimulating acid secretion 1, 2, 4.

  2. Hormonal mechanisms: Gastrin from G cells primarily acts on ECL cells to release histamine, which then stimulates parietal cells 5, 4.

  3. Paracrine mechanisms: Histamine from enterochromaffin-like (ECL) cells acts on H2 receptors on parietal cells, activating adenylate cyclase and generating cAMP to stimulate acid secretion 1, 2.

  4. Inhibitory mechanisms: Somatostatin from D cells inhibits acid secretion by acting on receptors coupled to inhibition of adenylate cyclase 1, 2.

All these pathways converge on the H+K+ ATPase (proton pump), which is the final common pathway for acid secretion 1, 2.

Clinical Implications

Understanding the mechanisms of gastric acid secretion is crucial for:

  • Appropriate use of acid-suppressing medications: H2-receptor antagonists and proton pump inhibitors are commonly used to reduce gastric acid secretion in conditions like GERD and peptic ulcer disease 6.

  • Management of short bowel syndrome: H2-receptor antagonists or proton pump inhibitors are recommended to reduce fecal wet weight and sodium excretion, especially during the first six months after surgery 6.

  • Prevention of bisphosphonate-related gastric damage: Bisphosphonates can cause gastric irritation and should be taken with caution in patients with gastric disorders 6, 3.

References

Research

Pharmacology of gastric acid inhibition.

Bailliere's clinical gastroenterology, 1993

Research

Control of gastric acid secretion:the gastrin-ECL cell-parietal cell axis.

Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 2001

Research

Gastric acid secretion.

Current opinion in gastroenterology, 2016

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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