GABAergic mechanisms of gastroprotection in the rat: role of sensory neurons, prostaglandins, and nitric oxide.
gamma-Aminobutyric acid (GABA) is a neurotransmitter found in both the central and the peripheral nervous systems including the gastrointestinal tract. The aims of the present studies were to examine mechanisms by which GABA exerts gastroprotective effects against ethanol- and water-restraint stress (WRS)-induced gastric mucosal injury in the rat. GABA, administered intragastrically (400 mg/kg), induced gastroprotection against ethanol and WRS by activating gastric sensory neurons to release calcitonin gene-related peptide (CGRP) and promote nitric oxide (NO) synthesis and release. Furthermore, these protective effects of GABA were associated with an increase in gastric mucosal blood flow (GMBF) that was dependent on sensory neuron and NO systems. GABA-mediated protection involved GABAA receptor activation and prostaglandin generation. In conclusion, intraluminal GABA protects the stomach against ethanol- and WRS-induced injury by mechanisms which involve sensory neuron/CGRP/NO pathways and increases in GMBF and prostaglandin generation.
Harty
Richard F
RF
Division of Gastroenterology, Department of Medicine, University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma, USA. richard-harty@ouhsc.edu
Ancha
Hanumantha R
HR
Xia
Yang
Y
Anderson
Mark
M
Jazzar
Ahmad
A
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D000431:Ethanol / Q000037:antagonists & inhibitors; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000503:physiopathology*; D013312:Stress, Physiological / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D018755:GABA Agonists; D018756:GABA Antagonists; D011453:Prostaglandins; D009569:Nitric Oxide; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D015740:Calcitonin Gene-Related Peptide