Vagal mechanisms underlying gastric protection induced by chemical activation of raphe pallidus in rats.
Peripheral mechanisms involved in kainic acid injected into the raphe pallidus (Rpa)-induced gastric protection were investigated in urethan-anesthetized rats. Gastric mucosal blood flow (GMBF), acid secretion, and gastric injury induced by intragastric ethanol (60%) were measured in response to kainic acid (25 pg) injected into the Rpa. Kainic acid reduced ethanol-induced gastric lesions by 57%. The protective effect was blocked by vagotomy, capsaicin deafferentation, and intravenous injection of the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) and NG-nitro-L-arginine methyl ester (L-NAME). L- but not D-arginine reversed the L-NAME action. Kainic acid injected into the Rpa, unlike outside sites, increased basal GMBF but not acid secretion. Indomethacin unmasked an acid secretory response to kainic acid. These results show that kainic acid injected into the Rpa at a dose that did not stimulate acid secretion, due to the inhibitory effect of prostaglandins, protects against ethanol-induced gastric injury through vagal-dependent activation of CGRP contained in capsaicin-sensitive afferents and nitric oxide-mediated gastric vasodilatory mechanisms.
Kaneko
H
H
Digestive Diseases Research Center, West Los Angeles Veterans Affairs Medical Center, Digestive Disease Division, Department of Medicine and Brain Research Institute, University of California, Los Angeles, California 90073, USA.
Kaunitz
J
J
Taché
Y
Y
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D000431:Ethanol; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D007608:Kainic Acid; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin