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.
Yang
H
H
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, USA. hoyang@ucla.edu
Kawakubo
K
K
Taché
Y
Y
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002799:Cholinergic Fibers / Q000502:physiology; D017097:Electric Impedance; D000431:Ethanol; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019894:Peptide YY / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000235:genetics; D013270:Stomach / Q000187:drug effects; D013272:Stomach Diseases / Q000139:chemically induced / Q000473:pathology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology
D016376:Oligonucleotides, Antisense; D018025:Receptors, Thyrotropin-Releasing Hormone; D019894:Peptide YY; D009569:Nitric Oxide; D000431:Ethanol; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D015740:Calcitonin Gene-Related Peptide; D011761:Pyrrolidonecarboxylic Acid