Central action of TRH to induce vagally mediated gastric cytoprotection and ulcer formation in rats.
The vagus nerve plays an important role in gastric cytoprotection and gastric lesion formation, but the central and peripheral mechanisms by which the vagus mediates these dual effects on the gastric mucosa are still not well established. Recent evidence indicates that the tri-amino acid peptide thyrotropin-releasing factor (TRH) acts in the brain, most likely in the dorsal vagal complex, and stimulates gastric vagal efferent discharges. Such increased vagal activity results in cholinergic stimulation of the gastric secretory and motor functions that influence the resistance of the gastric mucosa to injury. Low doses of TRH or its stable analogue, RX 77368 (0.5-1.5 ng), injected into the cisterna magna, confer cytoprotection against ethanol-induced gastric lesions through the vagal cholinergic stimulation of gastric prostaglandin release. After higher doses of RX 77368 (3-300 ng), cytoprotection is observed only when the associated increase in acid secretion is prevented by omeprazole. Intracisternal injection of RX 77368 at doses of 1-3 micrograms induces the development of acute gastric lesions within 4 h which are further enhanced by indomethacin in fasted rats. Gastric lesions are related to the vagally mediated sustained increase in gastric acid and pepsin secretion, motility, and vascular changes. These data, added to the neuroanatomic evidence of high concentrations of TRH fibers and receptors in the dorsal vagal complex, indicate that medullary TRH may play an important role in the central vagal regulation of gastric mucosal resistance. This mucosal resistance is influenced by the interaction between vagal-cholinergic activation of cytoprotective mechanisms (prostaglandin, increased gastric mucosal blood flow) and ulcerogenic factors (histamine, acid, pepsin, motility).
Taché
Y
Y
Center for Ulcer Research and Education, VA Medical Center, Los Angeles, California 90073.
Yoneda
M
M
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D002799:Cholinergic Fibers / Q000502:physiology; D015232:Dinoprostone / Q000502:physiology; D004525:Efferent Pathways / Q000503:physiopathology; D005753:Gastric Mucosa / Q000294:innervation*; D008526:Medulla Oblongata / Q000503:physiopathology; D051381:Rats; D013276:Stomach Ulcer / Q000503:physiopathology*; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*; D014630:Vagus Nerve / Q000503:physiopathology*
D013973:Thyrotropin-Releasing Hormone; D015232:Dinoprostone