Mechanosensitive ion channel Piezo1 is expressed in antral G cells of murine stomach

Kerstin Lang,Claudia Frick,Heinz Breer

doi:10.1007/s00441-017-2755-0

Kerstin Lang, Claudia Frick + Show 1 more

Open Access

https://doi.org/10.1007/s00441-017-2755-0

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Abstract

G cells in the antrum region of the murine stomach produce gastrin, the central hormone for controlling gastric activities. Secretion of gastrin is induced mainly by protein breakdown products but also by distensions of the stomach wall. Although G cells respond to protein fragments via distinct chemosensory receptor types, the mechanism underlying G cell activation upon distention is entirely ambiguous. Mechanosensitive ion channels are considered as potential candidates for such a task. Therefore, we explore the possibility of whether Piezo1, a polymodal sensor for diverse mechanical forces, is expressed in antral G cells. The experimental analyses revealed that the vast majority of G cells indeed expressed Piezo1. Within flask-like G cells at the base of the antral invaginations, the Piezo1 protein was primarily located at the basolateral portion, which is thought to be the release site for the exocytic secretion of gastrin. In the spindle-like G cells, which are oriented parallel to the invaginations, Piezo1 protein was restricted to the cell body where the hormone was also located, whereas the long processes appeared to be devoid of Piezo1 protein. Our results suggest that mechanosensitive channels such as Piezo1, located in close proximity to hormone-release sites, enable G cells to respond directly to antrum distensions with gastrin secretion.

Highlights

Endocrine cells in the gastrointestinal tract respond to a wide variety of stimuli including nutrients and non-nutrient factors such as pH and mechanical stimuli
After washes in 1 × phosphate-buffered saline (PBS), the bound primary antibodies were visualized by using donkey anti-rabbit IgG (H + L) secondary antibody bound to Alexa Fluor 568 (InvitrogenTM, Fisher Scientific, Göteborg, Sweden) and goat anti-guinea pig IgG (H + L) secondary antibody bound to Alexa Fluor 488
A direct response of G cells to mechanical stimuli is thought to be mediated by mechanosensitive ion channels, which are transmembrane proteins forming ion conduction pores gated by mechanical forces (Árnadóttir and Chalfie 2010)

Summary

Introduction

Endocrine cells in the gastrointestinal tract respond to a wide variety of stimuli including nutrients and non-nutrient factors such as pH and mechanical stimuli. G cells are almost exclusively located in the antral gastric mucosa and release gastrin in response to the luminal presence of partially digested proteins and to the distension of the stomach wall (Schiller et al 1980; Schubert and Makhlouf 1993). A more recent investigation revealed that, following antral denervation, the sensitivity of gastrin cells to distension is even increased (Higham et al 1997). Speculation that G cells possess intrinsic mechanosensitivity is tempting (Higham et al 1997) This notion suggests that G cells closely resemble enterochromaffin (EC) cells, which are well known as being stimulated to release 5-hydroxytryptamine by mechanical forces and which are considered important mechanosensors of the gastrointestinal epithelium (Bertrand 2004). Any evidence for the presence of mechanosensitive proteins that could render G

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