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 ⅐ kg Ϫ1 ⅐ h Ϫ1 ) 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 pmol⅐kg Ϫ1 ⅐h Ϫ1 ), whereas injected intracisternally (460 g/20 l), it significantly prevented

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... al 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 ⅐ kg Ϫ1 ⅐h Ϫ1 iv) significantly decreased ethanol-induced gastric lesions by 82%, whereas [Leu 31 , Pro 34 ]NPY, a Y1/Y3 agonist, and PYY-(3-36), a Y2 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. neuropeptide Y-receptor subtype; peptide YY antibody; vagotomy; ethanol; gastric lesions Address for reprint requests and other correspondence: Y. Taché, CURE: DDRC, VA GLAHS, Bldg. 115, Rm. 203, 11301 Wilshire Blvd.,