GO:1903640 negative regulation of gastrin-induced gastric acid secretion: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1903640 describes any process that stops, prevents, or reduces the frequency, rate, or extent of gastrin-induced gastric acid secretion.
• Cholecystokinin (CCK) is a key negative regulator of gastric acid secretion and postprandial gastrin release in humans.
• Secretin also inhibits gastric acid secretion, as demonstrated by classic physiological experiments.
• The term is a biological process node in the Gene Ontology, with synonyms including inhibition of gastrin-induced gastric acid secretion.
• Dysregulation of this process is linked to acid-related disorders such as peptic ulcer disease and gastroesophageal reflux disease.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable causal dissection of genes controlling this regulatory pathway.
Description
The Gene Ontology (GO) term GO:1903640, negative regulation of gastrin-induced gastric acid secretion, defines any biological process that stops, prevents, or reduces the frequency, rate, or extent of gastric acid secretion triggered by the hormone gastrin. This term captures a critical homeostatic mechanism in gastrointestinal physiology, where multiple hormonal and neural signals converge to fine-tune acid output. Understanding this process is essential for researchers studying acid-peptic disorders, neuroendocrine regulation, and the pharmacological control of gastric acidity. The regulation of gastric acid secretion involves a complex interplay between stimulatory hormones such as gastrin and inhibitory factors such as cholecystokinin (CCK) and secretin. CCK has been shown to act as a negative regulator of gastric acid secretion and postprandial release of gastrin in humans, highlighting its role in this GO term. Similarly, secretin, historically identified as an inhibitor of gastric acid secretion, provides a classic example of negative regulation. These findings underscore the importance of GO:1903640 in maintaining gastric mucosal integrity and preventing excessive acid exposure. For researchers, this term provides a framework to annotate genes and pathways that counteract gastrin-driven acid secretion, facilitating comparative genomics, functional enrichment, and drug target discovery.
negative regulation of gastrin-induced gastric acid secretion At A Glance
| GO ID | GO:1903640 |
|---|---|
| GO term | negative regulation of gastrin-induced gastric acid secretion |
| Ontology | biological_process |
| Synonym | down regulation of gastrin-induced gastric acid secretion; down-regulation of gastrin-induced gastric acid secretion; downregulation of gastrin-induced gastric acid secretion; inhibition of gastrin-induced gastric acid secretion |
| Major function | Inhibition or reduction of gastric acid secretion triggered by gastrin |
| Related hormones | Cholecystokinin (CCK), secretin |
| Physiological context | Postprandial regulation of gastric acidity |
| Research relevance | Target for acid-related diseases and pharmacological intervention |
What Is GO:1903640?
GO:1903640 is a biological process term defined as any process that stops, prevents, or reduces the frequency, rate, or extent of gastrin-induced gastric acid secretion. In other words, it encompasses the molecular and cellular events that inhibit the acid-secreting response triggered by the hormone gastrin. This includes hormonal feedback loops, paracrine signals, and neural pathways that ultimately suppress parietal cell activity or gastrin release.
Why Is negative regulation of gastrin-induced gastric acid secretion Important in Cell Biology?
GO:1903640 is important because it represents a key homeostatic mechanism that prevents excessive gastric acid secretion, which can damage the gastric mucosa and lead to peptic ulcers and reflux disease. Cholecystokinin and secretin are established negative regulators of gastric acid secretion in humans, and their actions are critical for postprandial acid control. Dysregulation of this process contributes to the pathogenesis of acid-peptic disorders, making it a focus for drug development and physiological research.
• Maintains gastric mucosal integrity by preventing acid overproduction.
• Cholecystokinin (CCK) negatively regulates gastrin-induced acid secretion in humans.
• Secretin is a classic inhibitor of gastric acid secretion.
• Dysregulation is linked to peptic ulcer disease and gastroesophageal reflux disease.
• Provides a target for pharmacological control of gastric acidity.
• Helps understand neuroendocrine feedback loops in the gut.
• Relevant to postprandial physiology and nutrient digestion.
• Guides CRISPR-based functional studies of regulatory genes.
• Supports biomarker discovery for acid-related disorders.
• Enables comparative analysis of acid regulation across species.
What Happens During negative regulation of gastrin-induced gastric acid secretion?
Gastrin Stimulation of Acid Secretion
In simple terms: Gastrin is a hormone that tells the stomach to make acid.
Gastrin, released by G cells in the stomach antrum, binds to CCK2 receptors on enterochromaffin-like (ECL) cells and parietal cells, stimulating histamine release and acid secretion. This step is the primary positive drive that negative regulation must counteract.
Cholecystokinin (CCK) as a Negative Regulator
In simple terms: CCK is a hormone that puts the brakes on acid production.
In humans, cholecystokinin (CCK) acts as a negative regulator of gastric acid secretion and postprandial release of gastrin. CCK is released from the small intestine in response to nutrients and inhibits gastrin-induced acid secretion, likely via CCK1 receptors on somatostatin-secreting D cells or directly on parietal cells.
Secretin Inhibition of Acid Secretion
In simple terms: Secretin is another hormone that reduces stomach acid.
Secretin, historically identified as an inhibitor of gastric acid secretion, is released from the duodenum in response to acidic chyme. It suppresses gastrin release and directly inhibits parietal cell acid production, as demonstrated in classic physiological experiments.
Somatostatin and Paracrine Inhibition
In simple terms: Somatostatin is a local signal that turns off acid-making cells.
Somatostatin, released by D cells in the stomach, acts in a paracrine manner to inhibit gastrin release from G cells and histamine release from ECL cells, thereby reducing gastrin-induced acid secretion. This pathway is a key component of negative regulation.
Neural and Hormonal Integration
In simple terms: Nerves and hormones work together to control acid.
The vagus nerve and enteric nervous system modulate acid secretion through acetylcholine and other neurotransmitters. Negative regulation involves the integration of inhibitory neural signals with hormonal feedback from CCK and secretin to fine-tune acid output.
Key Genes Involved in GO:1903640 negative regulation of gastrin-induced gastric acid secretion
The following genes and proteins are involved in the negative regulation of gastrin-induced gastric acid secretion, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CCK | Encodes cholecystokinin, a negative regulator of gastric acid secretion and gastrin release | Target for studying hormonal feedback in acid regulation |
| SCT | Encodes secretin, which inhibits gastric acid secretion | Classic model for inhibitory hormone action |
| SST | Encodes somatostatin, a paracrine inhibitor of gastrin and acid secretion | Key mediator of negative regulation |
| GAST | Encodes gastrin, the primary stimulator of acid secretion | Positive regulator counteracted by this process |
| CCKAR | CCK1 receptor, mediates CCK effects on acid secretion | Potential drug target for acid suppression |
| CCKBR | CCK2 receptor, binds gastrin and CCK | Central to gastrin signaling |
| HRH2 | Histamine H2 receptor, mediates histamine-stimulated acid secretion | Target of H2 blockers |
| ATP4A | Gastric H+/K+ ATPase alpha subunit, proton pump | Final effector of acid secretion |
| ATP4B | Gastric H+/K+ ATPase beta subunit | Component of proton pump |
| SLC26A3 | Chloride/bicarbonate exchanger, involved in acid-base balance | Indirectly affects acid secretion |
| CFTR | Chloride channel, may modulate acid secretion | Potential modifier |
| VIP | Vasoactive intestinal peptide, inhibits acid secretion | Neural inhibitor |
| NPY | Neuropeptide Y, inhibits acid secretion | Neural inhibitor |
| GAL | Galanin, inhibits acid secretion | Neural inhibitor |
| PYY | Peptide YY, inhibits gastric acid secretion | Gut hormone |
| GLP1R | GLP-1 receptor, may inhibit acid secretion | Incretin effect |
| OXT | Oxytocin, may inhibit acid secretion | Neuroendocrine modulator |
How Is negative regulation of gastrin-induced gastric acid secretion Regulated?
The negative regulation of gastrin-induced gastric acid secretion is itself regulated by multiple feedback loops. Cholecystokinin (CCK) release is stimulated by nutrients and acts as a negative regulator of both acid secretion and gastrin release. Secretin release is triggered by duodenal acidification and inhibits gastric acid secretion. Somatostatin, released from D cells, provides paracrine inhibition of G cells and ECL cells. These pathways are integrated with neural inputs from the vagus nerve, ensuring that acid secretion is appropriately suppressed when not needed.
negative regulation of gastrin-induced gastric acid secretion and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CCK | Peptic ulcer disease, GERD | CCK knockout mouse |
| SCT | Acid hypersecretion disorders | Secretin receptor knockout |
| SST | Peptic ulcer, H. pylori infection | Somatostatin knockout mouse |
| GAST | Zollinger-Ellison syndrome | Gastrin overexpression model |
| CCKAR | Acid-related disorders | CCK1 receptor point mutation |
Peptic Ulcer Disease
Impaired negative regulation of gastrin-induced acid secretion can lead to excessive acid production, contributing to peptic ulcer disease. Cholecystokinin and secretin deficiencies or resistance may exacerbate acid-peptic injury.
Gastroesophageal Reflux Disease (GERD)
Dysregulation of the inhibitory pathways that normally suppress gastrin-induced acid secretion can result in increased esophageal acid exposure and GERD symptoms. Understanding these mechanisms may inform new therapeutic strategies.
Zollinger-Ellison Syndrome
This syndrome is characterized by gastrin-secreting tumors (gastrinomas) that cause massive acid hypersecretion. The negative regulation of gastrin-induced acid secretion is overwhelmed, leading to severe ulcers and diarrhea.
Helicobacter pylori Infection
H. pylori infection alters gastrin and somatostatin regulation, disrupting the negative feedback loop and increasing acid secretion, which contributes to ulcer formation.
From negative regulation of gastrin-induced gastric acid secretion-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CCK negatively regulate gastrin-induced acid secretion? | CCK knockout mouse |
| What is the role of secretin in acid inhibition? | Secretin receptor knockout |
| How does somatostatin inhibit acid secretion? | Somatostatin conditional knockout |
| Can a point mutation in CCKAR alter acid regulation? | CCKAR point mutation knock-in |
| Does overexpression of CCK suppress acid secretion? | CCK overexpression transgenic |
| What genes are essential for negative regulation? | CRISPR library screening |
How to Study the negative regulation of gastrin-induced gastric acid secretion Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Intragastric titration | Gastric acid secretion rate | In vivo physiology |
| Isolated parietal cells | Acid production | In vitro mechanistic studies |
| Radioimmunoassay | Hormone concentrations | CCK, gastrin, secretin measurement |
| CRISPR knockout | Gene function loss | Causal gene discovery |
| CRISPR point mutation | Specific amino acid changes | Functional domain analysis |
| CRISPR knock-in | Tagged or reporter genes | Localization and tracking |
| Overexpression | Gain-of-function | Gene dosage effects |
Physiological Measurements of Gastric Acid Secretion
Gastric acid secretion can be measured in vivo using intragastric titration or in vitro using isolated parietal cells. These methods are essential to quantify the effects of negative regulators such as CCK and secretin.
Hormone Assays
Radioimmunoassays or ELISA for gastrin, CCK, and secretin in plasma or tissue culture media allow researchers to monitor hormonal changes during negative regulation.
CRISPR-Cas9 Gene Editing
Knockout, point mutation, knock-in, and overexpression models enable causal testing of candidate genes in the negative regulation pathway. These approaches can be applied in cell lines and animal models.
Transcriptomics and Proteomics
RNA-seq and proteomics can identify genes and proteins differentially expressed during negative regulation, providing unbiased insights into the molecular players involved.
How CRISPR Can Be Used to Study GO:1903640 negative regulation of gastrin-induced gastric acid secretion
Knockout
CRISPR knockout of candidate genes such as CCK, SCT, or SST can abolish negative regulation of gastrin-induced acid secretion, leading to acid hypersecretion. These models are valuable for target validation.
Point Mutation
Introducing point mutations in receptors like CCKAR or CCKBR can dissect the specific residues required for inhibitory signaling, providing mechanistic insights.
Knock-in
Knock-in of reporter tags (e.g., GFP) into genes such as SST or CCK allows real-time tracking of hormone release and cellular localization in the stomach.
Overexpression
Overexpression of negative regulators like CCK or secretin can suppress gastrin-induced acid secretion, offering a gain-of-function approach to study pathway dynamics.
How EDITGENE Supports negative regulation of gastrin-induced gastric acid secretion Research
Researchers studying negative regulation of gastrin-induced gastric acid secretion-related genes often need to determine whether a candidate gene is causally involved in suppressing acid output. EDITGENE provides comprehensive CRISPR services to accelerate this discovery.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of gastrin-induced gastric acid secretion research.
Frequently Asked Questions About negative regulation of gastrin-induced gastric acid secretion
What is GO:1903640?
GO:1903640 is a Gene Ontology biological process term for any process that stops, prevents, or reduces the frequency, rate, or extent of gastrin-induced gastric acid secretion.
What genes are involved in negative regulation of gastrin-induced gastric acid secretion?
Key genes include CCK (cholecystokinin), SCT (secretin), and SST (somatostatin), which act as negative regulators.
How does cholecystokinin inhibit gastric acid secretion?
Cholecystokinin (CCK) acts as a negative regulator of gastric acid secretion and postprandial gastrin release in humans, likely via CCK1 receptors.
What is the role of secretin in gastric acid regulation?
Secretin inhibits gastric acid secretion and was classically identified as an inhibitor in physiological experiments.
Which diseases are associated with dysregulation of this process?
Peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Ellison syndrome are linked to impaired negative regulation of gastrin-induced acid secretion.
How can CRISPR be used to study GO:1903640?
CRISPR knockout, point mutation, knock-in, and overexpression models allow causal testing of genes involved in this regulatory pathway.
What are the synonyms for GO:1903640?
Synonyms include down regulation of gastrin-induced gastric acid secretion, down-regulation of gastrin-induced gastric acid secretion, downregulation of gastrin-induced gastric acid secretion, and inhibition of gastrin-induced gastric acid secretion.
Why is negative regulation of gastrin-induced acid secretion important?
It prevents excessive acid production that can damage the stomach lining and cause ulcers.
What experimental models are used to study this process?
Models include CCK knockout mice, secretin receptor knockout, somatostatin conditional knockout, and CRISPR-engineered cell lines.
How does somatostatin contribute to this GO term?
Somatostatin acts as a paracrine inhibitor of gastrin and histamine release, thereby reducing gastrin-induced acid secretion.
Conclusion
GO:1903640, negative regulation of gastrin-induced gastric acid secretion, is a vital biological process that maintains gastric homeostasis by counteracting acid-stimulatory signals. Cholecystokinin and secretin are established negative regulators in humans, and their actions are critical for preventing acid-related diseases. Understanding this process at the molecular level offers opportunities for therapeutic intervention and requires robust experimental models. CRISPR-based approaches provide powerful tools to dissect the genes and pathways involved, and EDITGENE offers comprehensive services to support such research.
References
- 1. Schmidt WE et al.. 1994. Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans.. Gastroenterology 107(6):1610-20 PMID: 7958670
- 2. Walton KL. 2009. Teaching the role of secretin in the regulation of gastric acid secretion using a classic paper by Johnson and Grossman.. Adv Physiol Educ 33(3):165-8 PMID: 19745041
