Intracisternal PYY increases gastric mucosal resistance: role of cholinergic, CGRP, and NO pathways.

The influence of intracisternal injection of peptide YY (PYY) on gastric lesions induced by ethanol was studied in urethan-anesthetized rats. Gastric lesions covered 15-22% of the corpus as monitored 1 h after intragastric administration of 45% ethanol (5 ml/kg) in intracisternal vehicle control groups. PYY, at doses of 23, 47, or 117 pmol 30 min before ethanol, decreased gastric lesions by 27%, 63%, and 59%, respectively. Thyrotropin-releasing hormone (TRH) receptor antisense oligodeoxynucleotide pretreatment (intracisternally, 48 and 24 h before intracisternal PYY) did not influence the gastroprotective effect of intracisternal PYY (47 pmol) but abolished that of intracisternal TRH analog RX-77368 (4 pmol). RX-77368 (2.6 pmol) and PYY (6 pmol) were ineffective when injected intracisternally alone but reduced ethanol lesions by 44% when injected simultaneously. Atropine (subcutaneously), the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (intravenously), or the nitric oxide (NO) synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME, intravenously) completely abolished the gastroprotective effect of intracisternal PYY (47 pmol), whereas indomethacin (intraperitoneally) had no effect. The l-NAME action was reversed by l-arginine but not by d-arginine (intravenously). These results suggest that intracisternal PYY acts independently of medullary TRH to decrease ethanol-induced gastric lesions. The PYY action involves vagal cholinergic-mediated CGRP/NO protective mechanisms.