Chronic Alcohol Consumption Affects Gastrointestinal Motility and Reduces the Proportion of Neuronal NOS‐Immunoreactive Myenteric Neurons in the Murine Jejunum

Abstract

Alcohol consumption interferes with gastrointestinal transit causing symptoms in alcoholic patients. Nitric oxide (NO), synthesized by neuronal nitric oxide synthase (nNOS) plays an important role in the control of gastrointestinal motility. Our aim was to investigate whether chronic alcohol intake in a murine model induces gastrointestinal motility disturbances and affects the nitrergic myenteric neurons in the stomach and jejunum. Gastric emptying, small intestinal transit and geometric centre were measured in vivo after intragastric gavage of Evans blue. Nitrergic relaxations to electrical field stimulation (EFS) and exogenous NO were recorded in jejunal muscle strips in vitro. The proportion of nNOS-immunopositive myenteric neurons was assessed using PGP9.5 and nNOS immunostaining. After chronic alcohol consumption, gastric emptying and small intestinal transit were delayed compared with control mice, and the nitrergic nervemediated relaxations to EFS in the jejunum were decreased, whereas relaxations to exogenous NO did not differ. The proportion of nNOS-immunoreactive neurons did not change in the stomach, whereas in the jejunum the percentage decreased from 33% to 27% (P < 0.001) after chronic alcohol intake. The total number of myenteric neurons remained unchanged. These results suggest that chronic alcohol consumption disturbs gastric and small intestinal motility in vivo and in vitro and is associated with a decrease in the proportion of nNOS-immunoreactive myenteric neurons in the murine jejunum. Anat Rec, 293:1536Rec, 293: -1542Rec, 293: , 2010.

Relationship Between Patterns of Alcohol Consumption and Gastrointestinal Symptoms Among Patients With Irritable Bowel Syndrome

“…Alcohol decreases gastric motility in mice. 13 In the small intestine, alcohol decreases the impedance wave motility (muscles that retain food for further digestion) but does not affect the propulsive wave motility (movements that propel food within the intestine) contributing to diarrhea seen in individuals who chronically consume alcohol. 14,15 Alcohol has also been shown to increase intestinal permeability in both animals and humans.…”

Diabetes-related alterations in the enteric nervous system and its microenvironment

“…Various reports have described the plastic remodeling of the nitrergic neurons during development [55,58,59] , aging [60] and pathological conditions [22,61] . Several studies have suggested that nitrergic myenteric neurons are especially susceptible to the development of neuropathy in digestive tract diseases, like diabetes [22,[62][63][64][65] , chronic ethanol consumption [66][67][68] and inflammation [69] .…”

Chronic alcohol consumption induces an overproduction of NO by nNOS- and iNOS-expressing myenteric neurons in the murine small intestine

“…Chronic intake of alcohol severely affects organs of the body by altering signaling pathways and the function of various cell types. In the gastrointestinal (GI) tract of man 1–3 and experimental animals, 4–6 chronic alcohol consumption (CAC) prominently disturbs normal intestinal motor function leading to motility disturbances 7 . There is some evidence that these motor disturbances are caused by an effect of ethanol on the nitric oxide (NO) system of relaxation in the gut 6,8,9 .…”

“…In the gastrointestinal (GI) tract of man 1–3 and experimental animals, 4–6 chronic alcohol consumption (CAC) prominently disturbs normal intestinal motor function leading to motility disturbances 7 . There is some evidence that these motor disturbances are caused by an effect of ethanol on the nitric oxide (NO) system of relaxation in the gut 6,8,9 . In the GI tract, NO produced by enteric neurons is involved in the regulation of motility, secretion and blood flow 10–12 .…”