Histamine is involved in gastric vasodilation during acid back diffusion via activation of sensory neurons

Abstract

Protective vasodilation during acid back diffusion into the rat gastric mucosa depends on activation of sensory neurons and mast cell degranulation with histamine release. We hypothesized that these two mediator systems interact and that histamine partly exerts its effect via sensory nerves. Gastric blood flow (GBF) and luminal histamine were measured in chambered stomachs, and mast cell numbers were assessed by morphometry. Ablation of sensory neurons and depletion of mast cells were produced by pretreatment with capsaicin or dexamethasone, respectively. Mucosal exposure to 1.5 M NaCl and then to pH 1.0 saline in ablated and control rats caused increased luminal histamine and reduced numbers of mast cells. Enterochromaffin-like cell marker pancreastatin remained unchanged. Only control rats responded with an increase in GBF. Capsaicin stimulation (640 microM) of the undamaged mucosa induced identical increase in GBF and unchanged mast cell mass in normal and dexamethasone-treated rats. Increase in GBF after topical exposure to histamine (30 mM) in rats pretreated with capsaicin or a calcitonin gene-related peptide (CGRP)(1) antagonist human CGRP(8-37) or exposed to the calcium pore blocker ruthenium red was less than one-half of that in control rats. These data suggest that mast cell-derived histamine is involved in gastric vasodilatation during acid back diffusion partly via sensory neurons.

Discovery and Mechanism of Gastroprotective Action of Capsaicin

“…Recently it has been reported, that mast cell deficient Sash mice are highly susceptible to piroxicam-induced gastric ulceration. Thus, it seems that beyond the potent gastroprotective effect of capsaicin-sensitive nerve endings described earlier and presented in humans (Mózsik et al,2014 in this volume) mast cells play also role through releasing vasodilator mediators (Rydning et al, 2002), but by releasing histamine it enhances on H 2 receptors gastric acid secretion which in these mice did not interfere with the ulcer formation (Hampton and Hale, 2013).…”

What We Know and What We Need to Know about Aromatic and Cationic Biogenic Amines in the Gastrointestinal Tract

“…It has been proposed recently that HIS could also inhibit its own secretion through binding to H 3 R present in ECL cells membranes [ 17 ]. Acting through other receptors, HIS has also been proposed as involved in the gastric vasodilatation and reactive hyperaemia produced in response to acid challenge (through H 1 R), and the modulation of the gastric mucosal defence, the enteric neurotransmission and the feedback regulation of HIS release (through H 3 R, and maybe also through H 4 R) [ 73 , 74 ]. Nevertheless, the precise roles of H 4 R in gastric physiology are still controversial [ 75 ].…”

Functional human gastrointestinal organoids can be engineered from three primary germ layers derived separately from pluripotent stem cells

“…These diverse cell types are required for proper execution of the GI tract's complex functions. For example, the key functions of the stomach to chemically and mechanically break down orally ingested nutrients depend on a complex interaction of the epithelium to produce acid and proteases (Furness et al, 2020;Zhao et al, 2008;Norle ´n et al, 2005;Rydning et al, 2002), smooth muscle to contract and relax, and enteric nerves to coordinate both of these processes (Sung et al, 2018;Beckett et al, 2017;Shaylor et al, 2016;Li et al, 2011). These three main components of the stomach develop separately from the three primary germ layers but then assemble into a tissue that is functional by birth, with the endoderm forming the epithelial lining, the mesoderm contributing to stromal cells and smooth muscle layers, and the ectoderm giving rise to the enteric nervous system (ENS).…”