Medullary TRH is involved in gastric protection induced by low dose of kainic acid into the raphe pallidus.
The gastroprotective effect of kainic acid microinjected into the raphe pallidus (Rpa) at a dose subthreshold to increase acid secretion was investigated in urethan-anesthetized rats. Kainic acid (25 pg/30 nl) microinjected into the Rpa inhibited by 65.8% gastric damage induced by intragastric ethanol (60%). No protection was observed when kainic acid was injected outside of the Rpa. The cytoprotective effect was completely abolished by thyrotropin-releasing hormone (TRH) antibody microinjected bilaterally (1.3 micrograms/site) into the dorsal motor nucleus of the vagus (DMN), indomethacin (5 mg/kg ip), and atropine (0.3 mg/kg sc). Microinjection of TRH antibody outside of the DMN or of control antibody into the DMN did not modify the protective action induced by kainic acid into the Rpa. The TRH antibody microinjected alone into the DMN did not alter the severity of the ethanol-induced gastric lesions. These data indicate that excitation of Rpa neurons by a low dose of kainic acid results in cytoprotection against ethanol lesions. Furthermore, this cytoprotection occurs as a result of TRH action in the DMN and activation of muscarinic and prostaglandin pathways.
Kaneko
H
H
Center for Ulcer Research and Education/Gastroenteric Biology Center, Veterans Affairs Wadsworth Medical Center, Los Angeles, California 90073.
Yang
H
H
Ohning
G
G
Taché
Y
Y
D000818:Animals; D000906:Antibodies / Q000276:immunology; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005917:Globus Pallidus / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D008845:Microinjections; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D013973:Thyrotropin-Releasing Hormone; D007608:Kainic Acid