Central thyrotropin-releasing factor analog prevents ethanol-induced gastric damage through prostaglandins in rats. 1992

M Yoneda, and Y Taché
Center for Ulcer Research and Education, Veterans Administration Medical Center, Los Angeles, California.

The effects of intracisternal injection of the stable thyrotropin-releasing factor (TRH) analog RX 77368 on gastric lesions induced by 60% ethanol and gastric prostaglandin E2 (PGE2) release were studied in rats. RX 77368 (1.0 and 1.5 ng) injected intracisternally inhibited (by 58% and 78%, respectively) macroscopic gastric damage induced by ethanol. Higher doses (3 and 300 ng) inhibited ethanol-induced gastric injury only in rats pretreated with omeprazole (20 mg/kg SC). Gastric acid output measured in conscious rats 2 hours after pylorus ligation was not modified by intracisternal injection of RX 77368 at 1.5 ng but was significantly increased by 54% at the 3-ng dose. The protective effect of TRH analog (1.5 ng) was completely abolished by indomethacin (5 mg/kg IP) and atropine (2 mg/kg SC) pretreatment. In pylorus-ligated rats, intracisternal RX 77368 (1.5 ng) inhibited ethanol-induced gastric lesions by 64%. Intracisternal injection of RX 77368 (1.5 ng) increased PGE2 levels measured in the effluent of dialysis fibers implanted into the corpus submucosa of urethane-anesthetized rats. Peripheral administration of omeprazole, atropine, indomethacin, or RX 77368 (1.5 ng IV) did not influence gastric damage induced by ethanol. These data show that the stable TRH analog, RX 77368, injected intracisternally at low non-secretory doses acts in the brain to protect against ethanol lesions through prostaglandin and cholinergic pathways. These findings suggest that central vagal activation induced by TRH may play a role in the control of mucosal integrity against ethanol through cholinergic prostaglandin release.

UI MeSH Term Description Entries
D008297 Male Males
D011761 Pyrrolidonecarboxylic Acid A cyclized derivative of L-GLUTAMIC ACID. Elevated blood levels may be associated with problems of GLUTAMINE or GLUTATHIONE metabolism. 5-Oxoproline,Pidolic Acid,Pyroglutamic Acid,5-Ketoproline,5-Oxopyrrolidine-2-Carboxylic Acid,Magnesium Pidolate,Pyroglutamate,Pidolate, Magnesium
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D005744 Gastric Acid Hydrochloric acid present in GASTRIC JUICE. Hydrochloric Acid, Gastric,Acids, Gastric,Acids, Gastric Hydrochloric,Gastric Acids,Gastric Hydrochloric Acid,Gastric Hydrochloric Acids,Hydrochloric Acids, Gastric
D005753 Gastric Mucosa Lining of the STOMACH, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. The surface cells produce MUCUS that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the LAMINA PROPRIA at various region of the stomach (CARDIA; GASTRIC FUNDUS; and PYLORUS), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, HYDROCHLORIC ACID, or hormones. Cardiac Glands,Gastric Glands,Pyloric Glands,Cardiac Gland,Gastric Gland,Gastric Mucosas,Gland, Cardiac,Gland, Gastric,Gland, Pyloric,Glands, Cardiac,Glands, Gastric,Glands, Pyloric,Mucosa, Gastric,Mucosas, Gastric,Pyloric Gland
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013973 Thyrotropin-Releasing Hormone A tripeptide that stimulates the release of THYROTROPIN and PROLACTIN. It is synthesized by the neurons in the PARAVENTRICULAR NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, TRH (was called TRF) stimulates the release of TSH and PRL from the ANTERIOR PITUITARY GLAND. Protirelin,Thyroliberin,Abbott-38579,Antepan,Proterelin Tartrate,Proterelin Tartrate Hydrate,Protirelin Tartrate (1:1),Relefact TRH,Stimu-TSH,TRH Ferring,TRH Prem,Thypinone,Thyroliberin TRH Merck,Thyrotropin-Releasing Factor,Thyrotropin-Releasing Hormone Tartrate,Abbott 38579,Abbott38579,Hydrate, Proterelin Tartrate,Prem, TRH,Stimu TSH,StimuTSH,TRH, Relefact,Tartrate Hydrate, Proterelin,Thyrotropin Releasing Factor,Thyrotropin Releasing Hormone,Thyrotropin Releasing Hormone Tartrate
D014630 Vagus Nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Cranial Nerve X,Pneumogastric Nerve,Tenth Cranial Nerve,Nerve X,Nervus Vagus,Cranial Nerve, Tenth,Cranial Nerves, Tenth,Nerve X, Cranial,Nerve Xs,Nerve, Pneumogastric,Nerve, Tenth Cranial,Nerve, Vagus,Nerves, Pneumogastric,Nerves, Tenth Cranial,Nerves, Vagus,Pneumogastric Nerves,Tenth Cranial Nerves,Vagus Nerves,Vagus, Nervus

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