Gastric protective effect of peripheral PYY through PYY preferring receptors in anesthetized rats

The influence of intravenous peptide YY (PYY) on the gastric injury induced by 45% ethanol was investigated in urethane-anesthetized rats. PYY (25, 75, 125, and 250 pmol x kg(-1) x h(-1)) significantly reduced gastric lesions by 36, 59, 40, and 38%, respectively. Antibody against ratPYY (2 mg/rat) injected intravenously completely prevented the gastroprotective effect of intravenous PYY (75 pmol x kg(-1) x h(-1)), whereas injected intracisternally (460 microg/20 microl), it significantly prevented intracisternal PYY (24 pmol/rat)-induced 58% reduction of ethanol lesions but not that induced by intravenous PYY. Vagotomy did not influence the gastroprotective effect of intravenous PYY. The Y(1)/"PYY-preferring" receptor agonist Pro(34)]PYY (75 pmol x kg(-1) x h(-1) iv) significantly decreased ethanol-induced gastric lesions by 82%, whereas Leu(31), Pro(34)]NPY, a Y(1)/Y(3) agonist, and PYY-(3-36), a Y(2) agonist, had no effect. These data indicate that PYY-infused intravenously at doses reported to mimic postprandial peak blood levels prevents ethanol-induced gastric injury through vagal independent pathways and PYY-preferring receptors.