G CELLS: DEVELOPMENT, GASTRIN, PIEZO MECHANOSENSITIVE CHANNELS - BIOLOGY - 2025

The G cells are endocrine cells that are subject to humoral and neural regulation luminal contents. They are located at the level of the duodenal mucosa and the gastric antrum. These cells represent a minor percentage of the cells of the gastric mucosa (1%).

The microvilli present in this cell type, which are distributed on their apical surfaces, make it possible to take samples of gastric contents. G cells release gastrin, which is a polypeptide hormone whose secretion is induced by stimuli of a neural, mechanical, or chemical nature.

G cell of the gastric antrum. By Miguelferig, from Wikimedia Commons.

Gastrin stimulates the parietal cells to secrete acid, increases blood flow in the gastric mucosa, induces the secretion of pepsin in the main cells, and promotes the growth of exocrine and pancreatic tissue, as well as gastric motility.

The activity or mechanism of action of G cells is stimulated by the presence of protein degradation products. However, it has been shown that they not only respond to these types of chemical signals, but are also stimulated by distention of the abdominal wall.

In this sense, the presence of mechanosensitive ion channels belonging to the Piezo family has been evidenced, which are described later.

G cell development

In vertebrates, the stomach fulfills multiple functions in addition to being the place where food is stored, such as providing a barrier that prevents the entry of microorganisms into the intestine and creating a protective environment against attacks of an endogenous or exogenous nature.

The stomach has various cells, which perform specific functions. Such is the case of enterochromaffin cells responsible for producing histamine; cells that secrete hormones of a peptide nature; D cells that release somatostatin; ghrelin-producing A cells; and G cells that secrete gastrin.

G cells originate from pre-endocrine hormonal cells that undergo asymmetric division in the lining of the stomach, giving rise to two daughter cells. One of them expresses somatostatin and the other expresses gastrin in each division process.

Such asymmetric division enables somatostatin-secreting cells to modulate the growth and action of gastrin-secreting G cells. The maturation of both cell types is finely regulated by transcription factors.

Gastrin and cholecystokinin receptor

Gastrin release by the G cells of the antrum of the gastric mucosa. By Adam L. VanWert, Pharm.D., Ph.D., from Wikimedia Commons.

Gastrin in principle is translated as preprogastrin. Once the translation process has occurred, the preprogastrin undergoes cleavages that originate peptides of different sizes, in which "Big" gastrin is the most common peptide.

The biological activity of gastrin is found in a sequence called pentagastrin, which is made up of 5 amino acids. This sequence is located in the C-terminal domain.

The actions of gastrin occur subsequent to its binding to the cholecystokinin receptor (CCKB), a G protein-coupled receptor.

Once gastrin binds to its receptor, a signaling cascade is triggered in which membrane inositols such as phospholipase C are activated, which leads to increases in intracellular calcium concentrations and the action of second messengers such as inositol triphosphate and diacylglycerol.

However, this receptor can also induce activation of the signaling pathway that involves tyrosine kinase receptors, only to a lesser extent.

The expression of the CCKB receptor is found in the digestive system, white blood cells, endothelial cells, and the central nervous system.

Piezo mechanosensitive channels

Mechanosensitive ion channels respond to mechanical impulses, that is; they open when the cell membrane is subjected to a change in tension or pressure.

The mechanisms through which these changes are perceived are under discussion, but the participation of components of the cytoskeleton and phospholipases associated with the cell membrane has been proposed.

Piezo mechanosensitive channels are proteins that have been conserved throughout evolution and that, in addition to being voltage modulated, respond to stimuli of a mechanical nature.

The Piezo1 and Piezo2 ion channels fulfill a wide range of physiological processes of vital importance. For example: Piezo1, participates in the development of the lymphatic system and the vasculature in mice.

Piezo 2, for its part, participates in the mechanotransduction of Merkel cells and sensory neurons located in the dorsal root.

Recent studies in humans and mice have shown that Piezo channels are also involved in non-sensory physiological processes such as remodeling of smooth muscle, formation of the epithelial lamina and cartilage in the cells that compose it (chondrocytes).

In mice it has been shown that deletion of the Piezo 1 or Piezo 2 genes leads to embryo mortality or early postnatal lethality.

Expression of mechanosensitive channels in G cells

The G-cell responses to the various protein products is carried out by chemosensory receptors. However, the mechanisms involved in the activation of these cells after distention of the stomach wall are poorly understood.

Antral innervation is required for G-cell stimulation to occur. However, a recent study indicated that even after antral denervation, G-cell action increases in response to distention. That is why it has been speculated that G cells are sensitive to mechanical stimuli.

In view of this, a group of researchers set out to elucidate the existence of Piezo ion channels in G cells, which are mechanosensitive. The results obtained effectively demonstrated that Piezo 1 channels are expressed in the antral region of the stomach of mice.

Piezo 1 channels are not evenly distributed throughout the G cell, but rather in the basolateral part. Fact that is of great interest since gastrin storage in secretory vesicles occurs precisely in that region, awaiting the arrival of the appropriate stimulus for its release.

References

1. Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010; 330: 55-60.
2. Frick C, Rettenberger AT, Lunz ML, Breer H. Complex morphology of gastrin-releasing G-cells in the antral region of the mouse stomach. Cell Tissue Res. 2016; 366 (2): 301-310.
3. Jain R, Samuelson L. Differentiation of the Gastric Mucosa. II Role of gastrin in gastric epithelial cell proliferation and maturation. Am J Physiol Gastrointest Liver Physiol. 2006; 291: 762-765.
4. Kasper D, Fauci A, Longo D, Braunwald E, Hauser S, Jameson J. (2005). Harrison, Principles of Internal Medicine. (16th ed.). Mexico: McGrawHill.
5. Lang K, Breer H, Frick. Mechanosensitive ion channel Piezo1 is expressed in antral G cells of murine stomach. Cell Tissue Res. 2018; 371 (2): 251-260.
6. Moroni M, Servin-Vences R, Fleischer R, Sánchez-Carranza O, Lewin GR. Voltage gating of mechanosensitive PIEZO channels. Nat Commun. 2018; 9 (1): 1096. doi: 10.1038 / s41467-018-03502-7
7. Phillison M, Johansson M, Henriksnas J, Petersson J, Gendler S, Sandler S, Persson E, Hansson G, Holm L. The gastric mucus layers: constituents and regulation of accumulation. Am J Physiol Gastrointest Liver Physiol. 2008; 295: 806-812.
8. Raybould H. Does Your Gut Taste? Sensory Transduction in the Gastrointestinal Tract. News Physiol Sci. 1998; 13: 275-280.
9. Schiller LR, Walsh JH, Feldman M. Distention-induced gastrin release: effects of luminal acidification and intravenous atropine. Gastroenterology. 1980; 78: 912-917.