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CURE: Digestive Diseases Research Center, West Los Angeles Veterans Affairs Medical Center, and Department of Medicine, Digestive Diseases Division and Brain Research Institute, University of California, Los Angeles, California, 90073
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
NG-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.
thyrotropin-releasing hormone receptor antisense
oligodeoxynucleotides; prostaglandins; ethanol; calcitonin gene-related
peptide-(8
37); RX-77368; gastric lesions; peptide YY; nitric oxide
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