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Am J Physiol Gastrointest Liver Physiol 283: G1035-G1041, 2002. First published August 7, 2002; doi:10.1152/ajpgi.00154.2002
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Vol. 283, Issue 5, G1035-G1041, November 2002

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

Keishi Kawakubo, Hong Yang, and Yvette Taché

CURE: Digestive Diseases Research Center, Veteran's Affairs Greater Los Angeles Healthcare System, Department of Medicine, Division of Digestive Diseases and Brain Research Institute, University of California Los Angeles, Los Angeles, California 90073

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 · kg-1 · 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 · kg-1 · h-1), whereas injected intracisternally (460 µg/20 µl), 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 Y1/"PYY-preferring" receptor agonist [Pro34]PYY (75 pmol · kg-1 ·h-1 iv) significantly decreased ethanol-induced gastric lesions by 82%, whereas [Leu31, Pro34]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


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