Role of prostaglandins and calcitonin gene-related peptide in central vagal cholinergic-dependent protection against gastric injury in urethane-anesthetized rats.
The influence of central vagal activation induced by the thyrotropin-releasing hormone (TRH) analog, RX 77368, injected intracisternally on gastric mucosal injury produced by 60% ethanol (4 ml.kg-1) was investigated in urethane-anesthetized rats. RX 77368 (3, 10 and 30 ng) inhibits dose dependently macroscopic gastric damage induced by intragastric administration of 60% ethanol by 18, 43 and 77%, respectively. The cytoprotective effect of intracisternal RX 77368 (30 ng) was completely blocked by cervical vagotomy, atropine (2 mg.kg-1 s.c.), and CGRP8-37 (100 micrograms.kg-1 i.v.) and partially inhibited by indomethacin (5 mg.kg-1 i.p.). Vagotomy, atropine, indomethacin and CGRP8-37 alone did not modify gastric mucosal lesions induced by ethanol in rats injected intracisternally with saline. The present data show that intracisternal injection of TRH analog in urethane-anesthetized rats protects against ethanol-induced gastric injury through vagal cholinergic dependent pathways which recruit prostaglandins and CGRP mechanisms.
Kato
K
K
CURE/Digestive Disease Research Center, West Los Angeles VA Medical Center, CA 90073, USA.
Yang
H
H
Taché
Y
Y
D000758:Anesthesia; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D000431:Ethanol; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014520:Urethane; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D011453:Prostaglandins; D014520:Urethane; D000431:Ethanol; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D001285:Atropine; D015740:Calcitonin Gene-Related Peptide; D011761:Pyrrolidonecarboxylic Acid; D007213:Indomethacin