Parietal cell activation by arborization of ECL cell cytoplasmic projections is likely the mechanism for histamine induced secretion of hydrochloric acid

Abstract

Background and aims. Enterochromaffin-like (ECL) cells are central in the regulation of acid secretion. G cells release gastrin and activate ECL cell histamine secretion which stimulates parietal cell H₂ receptors initiating acid secretion. It is unclear whether histamine-mediated parietal cell activation is via a vascular or paracrine pathway. To assess this, we utilized immunohistochemistry (IHC) and electron microscopy to examine gastric tissue and used visualization of formalin fixed dispersed gastric cells and glands to investigate and define the anatomical relationship between ECL and parietal cells. Material and methods. Sprague–Dawley rat stomachs were instilled with formalin. Thereafter fixed mucosal cells and whole gastric glands were dispersed by mechanical and chemical dissolution and enzymatic digestion. Smears with fixed isolated cells and whole glands were stained by IHC with histidine decarboxylase (HDC) and H⁺/K⁺-ATPase antibodies. Whole tissue samples of Sprague–Dawley and cotton rat oxyntic mucosa were investigated with IHC using HDC, VMAT2 and H⁺/K⁺-ATPase antibodies, and electron microscopy was performed to further delineate the precise anatomic relationship between ECL cells and parietal cells. Results. Each ECL cell generated a network of HDC- and VMAT2-positive dendritic-like elongations that were in direct contact with several parietal cells. Thus, ECL cells at the base of the gland were in communication with parietal cells in the middle of the gland. Electron microscopy confirmed that the cytoplasmic ECL cell elongations containing secretory vesicles were in direct juxtaposition to parietal cells. Conclusions. These findings indicate that ECL cells directly regulate parietal cell function in a neurocrine manner via slender neuron-like elongations.

Key Words::

• Acid secretion
• enterochromaffin-like cell
• gastrin
• histamine
• neuroendocrine
• parietal cell

Acknowledgements

This study was supported by Oddrun Mjålands foundation and foundations for medical research at Trondheim University Hospital. We thank Nan Skogaker for technical assistance.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.