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 CGRP(8-37) (100 mu g . kg(-1) i.v.) and partially inhibited by indomethacin (5 mg . kg(-1) i.p.). Vagotomy, atropine, indomethacin and CGRP(8-37) 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.