{'fraction_non_alphanumeric': 0.028176501860712386, 'fraction_numerical': 0.01541733120680489, 'mean_word_length': 5.4673539518900345, 'pattern_counts': {'":': 0, '<': 4, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Ammonia Modulates Enteric Neuromuscular Transmission in the Mouse, Pig, and Human Intestine.

Ammonia is a waste product of protein metabolism that is primarily produced by gut bacteria. Accumulation of ammonia occurs in many metabolic disorders and the neurotoxic effects of ammonia can cause severe nervous system dysfunction. Our objective was to test the hypothesis that local buildup of ammonia alters neuromuscular control of intestinal function. The effects of ammonia on neurogenic relaxations and contractions evoked by electrical field stimulation (EFS; 2‐30 Hz, 0.5 ms, 20 V) and pharmacologic agents were studied in segments of mouse, pig and human small intestine in vitro using isometric tension recordings. Specific effects of ammonia on enteric neurons and glia were studied using in situ Ca2+ imaging of mouse ileal myenteric plexus. Ammonia increased carbachol induced longitudinal muscle contractions in small intestine segments of all species (p<0.05 all groups). EFS induced frequency‐dependent contractions and relaxations that were abolished by tetrodotoxin (TTX, 0.3 μM) (p<0.001 all groups). The amplitude of EFS evoked ileal and jejunal longitudinal muscle contractions were larger in the presence of ammonia and relaxations (10 μM scopolamine tone) were reduced in the presence of ammonia in all groups as compared to control (p<0.05 all groups). The enhanced excitatory response was significantly attenuated, but not abolished by PAPA NONOate (100 μM), a nitric oxide donor (P<0.05 human jejunum). Visualization of cellular activity in the mouse ileal myenteric plexus with Ca2+ imaging revealed that enteric glial cells are activated by ammonia. Our data support the hypothesis that ammonia toxicity in human, porcine, and murine small intestine disrupts nitrergic inhibitory neuromuscular transmission leading to increased smooth muscle contractility.