In Pursuit of the Parietal Cell - An Evolution of Scientific Methodology and Techniques

Abstract

The stomach has unique embryologic and anatomic properties, making the study of the parietal cell technically challenging. Numerous individuals have devoted decades of research to unraveling the pathophysiological basis of this cell type. Here, we perform a scoping review of novel in vitro and in vivo methodology pertaining to the parietal cell. First, we evaluate early in vitro methods of parietal cell analysis. This section focuses on three major techniques: gastric gland isolation, parietal cell isolation, and parietal cell culture. We also discuss parietal cell physiology and pathophysiology. Second, we discuss more contemporary efforts involving confocal microscopy and gastric organoids, a new technique that holds much promise in unveiling the temporal-spatial dynamics of the cell. Finally, we will discuss findings from our laboratory where we identified an active gastric vacuolar H⁺-ATPase as a putative mechanism for refractory GERD. Overall, this review aims to highlight the major milestones in understanding an elusive yet important cell. Though in no way comprehensive, we hope to provide a birds-eye view to the study of this unique cell type in the gastrointestinal tract.

Keywords: gastric gland isolation; in vitro techniques; in vivo confocal imaging; methodology; parietal cell.

FIGURE 1

Schematic representations of the stomach (A) and oxyntic gland (B). (A) The stomach is divided into two functional regions, the oxyntic region (composed of the cardia, fundus, and corpus) and the pyloric region (composed of the antrum and pylorus). (B) A representative oxyntic gland from the oxyntic region of the stomach features a gastric pit, isthmus, neck, and base. A variety of stomach cell types exist, including parietal cells, enterochromaffin cells, and mucous cells.

FIGURE 2

Images of the human gastric gland (A). Phase contrast of the human gland at 40× Magnification (B). pH sensitive dye BCECF-selective loading in parietal cells (C). Pseudo color image of the parietal cells following stimulation with a secretagogue. All images acquired with a Olympus OM2 microscope.

FIGURE 3

Key Events and Studies Involving the Parietal Cell and Gastric Acid Production.

FIGURE 4

Schematic representations of the parietal cell (A) gastric acid stimulants (B) exchangers, transporters, channels. (A) The H, K ATPase is stimulated through three primary inputs: acetylcholine (ACh), gastrin, and histamine. ACh and gastrin bind to their receptors and trigger activation of phospholipase C (PLC), which converts PIP2 to IP3 and triggers release of Ca²⁺from the sarcoplasmic reticulum. This leads to downstream activation of the H, K ATPase. Histamine binds to the H2 receptor, triggering activation of adenylyl cyclase and activation of PKA. (B) Multiple apical and basolateral anion and cation movements occur to maintain the gradient and electroneutral transport of Hydrogen.

FIGURE 5

Pathophysiologic basis of gastric acid hypersecretion. Illustrated are selected examples of changes to physiological acid secretion. Lines a,b,c represent surgical transection lines for truncal, selective, and highly selective vagotomies. This reduces cholinergic input for acid secretion. Triangle d is the anatomical region where a gastrinoma is most likely to exist. A gastrinoma provides constitutively high levels of gastrin, leading to overactive parietal cells, and hyperplastic changes in morphology.